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Review article
Changing patterns of West Nile virus transmission:altered vector
competence and host susceptibility
Aaron C. BRAULT*,**
Center for Vector-Borne Diseases and Department of Pathology,
Microbiology and Immunology,School of Veterinary Medicine,
University of California, 5327 VM3A,
One Shields Ave, Davis, CA 95616, USA
(Received 4 February 2009; accepted 29 April 2009)
Abstract West Nile virus (WNV) is a flavivirus (Flaviviridae)
transmitted between Culex spp.mosquitoes and avian hosts. The virus
has dramatically expanded its geographic range in the past ten
years.Increases in global commerce, climate change, ecological
factors and the emergence of novel viralgenotypes likely play
significant roles in the emergence of this virus; however, the
exact mechanism andrelative importance of each is uncertain.
Previously WNV was primarily associated with febrile illness
ofchildren in endemic areas, but it was identified as a cause of
neurological disease in humans in 1994. Thismodulation in disease
presentation could be the result of the emergence of a more
virulent genotype as wellas the progression of the virus into areas
in which the age structure of immunologically nave individualsmakes
them more susceptible to severe neurological disease. Since its
introduction to North America in1999, a novel WNV genotype has been
identified that has been demonstrated to disseminate more
rapidlyand with greater efficiency at elevated temperatures than
the originally introduced strain, indicating thepotential
importance of temperature as a selective criteria for the emergence
of WNV genotypes withincreased vectorial capacity. Even prior to
the North American introduction, a mutation associated
withincreased replication in avian hosts, identified to be under
adaptive evolutionary pressure, has beenidentified, indicating that
adaptation for increased replication within vertebrate hosts could
play a role inincreased transmission efficiency. Although stable in
its evolutionary structure, WNV has demonstrated thecapacity for
rapidly adapting to both vertebrate hosts and invertebrate vectors
and will likely continue toexploit novel ecological niches as it
adapts to novel transmission foci.
West Nile virus / vector competence / temperature / host
competence / virus-host interaction
Table of contents
1.
Introduction...........................................................................................................................................
21.1. Viral classification
.......................................................................................................................
21.2. Structure and
replication..............................................................................................................
21.3. Molecular epidemiology of
WNV...............................................................................................
31.4. Disease and
distribution...............................................................................................................
31.5. Transmission of
WNV.................................................................................................................
41.6. Use of crow mortality to track WNV activity
............................................................................
61.7. Virulence and immunity studies with
WNV...............................................................................
6
* Corresponding author: [email protected], [email protected]**
Current address: Division of Vector-Borne Infectious Diseases,
Centers for Disease Control andPrevention, 3150 Rampart
Rd/Foothills Campus, Fort Collins, CO 80521, USA
Vet. Res. (2009) 40:43DOI: 10.1051/vetres/2009026
INRA, EDP Sciences, 2009
www.vetres.org
noncommercial medium, provided the original work is properly
cited.
This is an Open Access article distributed under the terms of
the Creative Commons Attribution-Noncommercial
License(http://creativecommons.org/licenses/by-nc/3.0/), which
permits unrestricted use, distribution, and reproduction in any
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1. INTRODUCTION
The purpose of this review is to presentsome of the potential
factors that have beenassociated with the emergence of West
Nilevirus (WNV) from an endemic virus, generallyassociated with
childhood disease, to an agentthat has rapidly expanded its
geographic range,becoming established in the New World withnovel,
more serious disease manifestations.Ecological, virological,
epidemiological andentomological avenues are explored to
addressthis phenomenon.
1.1. Viral classification
West Nile virus is a member of the genusFlavivirus within the
family Flaviviridae [59]and was first isolated from a human
experienc-ing a febrile syndrome in the West Nile districtof Uganda
in 1937 [142]. Serological crossreactivity has grouped WNV within
the Japa-nese encephalitis (JE) virus serocomplex [27].In addition
to WNV, the JE serocomplexincludes three other viral species
respon-sible for human disease including Japaneseencephalitis
(JEV), St. Louis encephalitis(SLEV) and Murray Valley
encephalitis(MVEV) viruses [94].
Despite the name serocomplex, classifica-tion of these viruses
is based on a combinationof serological cross reactivity,
nucleotidesequence data, and vector association [59].The WNV
species contains one viral subtype(Kunjin), comprised of isolates
from Australia
and Malaysia [157]. West Nile viruses have apandemic
distribution having been isolated onevery continent with the
exception of Antarctica[57]. Despite the fact that serological
assays dis-tinguish WNV isolates from India as well asKunjin from
other WNV, only Kunjin is classi-fied as a distinct viral subtype
[156]. Nucleotidesequence data has subsequently demonstratedKunjin
viruses to have a greater genetic identitywith newly emergent WNV
genotypes than OldWorld strains including those from India
[115,135]. Altered serological reactivity is mostlikely due to the
lack of an additional glycosyl-ation motif within the envelope
glycoprotein ofKunjin viruses [1].
1.2. Structure and replication
West Nile virus is comprised of an envel-oped spherical virion
with a diameter ofapproximately 50 nm. The virus has a
linear,single-stranded, message-sense genome ofapproximately 11 Kb
with a 50(7-methyguano-sine) cap and no polyadenylation at the
30endof the genome [129]. The 50 and 30 non-codingregions (NCR)
have conserved nucleotide ele-ments that form stem-loop structures
necessaryfor viral RNA transcription, translation andpackaging [25,
72, 139]. Viral proteins aretranslated as a single polyprotein that
is post-translationally cleaved by host and viral prote-ases to
produce 3 structural (C, prM and E)and 7 nonstructural proteins
(NS1, NS2A,NS2B, NS3, NS4A, NS4B and NS5). The 50
third of the genome encodes the structural
2. Factors associated with West Nile viral
emergence.............................................................................
62.1. Virological factors associated with emergence
...........................................................................
6
2.1.1. Emergence of avian virulence
.........................................................................................
62.1.2. Genotype associated with avian virulence
......................................................................
72.1.3. Increased virulence as a factor for increased
transmission............................................. 82.1.4.
Viral adaptation for replication at higher
temperature....................................................
9
2.2. Environmental factors associated with
emergence......................................................................
102.2.1. Climate perturbation
........................................................................................................
102.2.2. Species diversity, species behavior and transmission
dynamics..................................... 102.2.3. Role of
heterologous flaviviruses on WNV transmission
.............................................. 112.2.4. Alternation
of transmission
patterns................................................................................
11
3. Conclusion
............................................................................................................................................
12
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proteins necessary for encapsidation of the viralRNA and the
surface proteins required for viralreceptor interaction and fusion
with host cells(Fig. 1) [76]. The remainder of the genomeencodes
the nonstructural proteins that formthe viral replication complex
for the generationof negative-sense template RNA as well
aspositive-sense genomic RNA [161]. The largestof the NS proteins,
NS3 and NS5, have beencharacterized for interactions and
replicaseactivity; however, the function of the remainingNS
proteins is largely unknown. The NS5protein has both RNA polymerase
and methyl-transferase motifs necessary for viral replica-tion.
Helicase and serine protease domainshave been described for the NS3
protein[129]. Interestingly, the NS1 protein is a secre-tory
nonstructural protein that does not have adesignated function in
RNA replication or asa control element [162].
1.3. Molecular epidemiology of WNV
Phylogenetic trees based on nucleotidesequence data indicate the
existence of fivepotentially distinct genetic lineages of WNVthat
have diverged by up to 29% at the nucleo-tide level [18, 89].
Sequence analysis of viralstrains from North America, Africa, the
MiddleEast, Asia, and Australia (Kunjin) constitutelineage 1 based
on structural [18, 63, 89] ornonstructural gene regions [14, 29].
Phyloge-netic analyses clearly indicate that Kunjin is amember of
lineage 1 and that the second line-age WNV, restricted to a
sub-Saharan Africandistribution, are more distantly related to
otherlineage 1 WNV than to Kunjin virus [135].Lineage 3 WNV is
represented by a CzechRepublic mosquito isolate (Rabensburg;
RabV)
[11], lineage 4 is comprised of Dermacentorspp. tick isolates
from the Russian Caucasus[117], and lineage 5 is represented by a
separategenotype from India [21]. Phylogenetic group-ing of
isolates does not correlate with geo-graphic distribution,
indicating the potentialimportance of birds in viral dispersal
[18].
All of the major outbreaks of human enceph-alitis have been
associated with viruses geneti-cally categorized as lineage 1,
making animportant correlation between viral geneticsand disease
phenotype. The preponderance ofgenetic evidence suggests that the
introductionof WNV into North America occurred fromthe Middle East.
Complete genomic sequencingof an isolate from an outbreak in geese
in Israelin 1998 and NY99 strains of WNV group themin the same
genetic clade with a 99.7% sharednucleotide identity [29, 90]. The
identificationof bird carcasses found to be positive forWNV from a
number of species in Israel pro-vides evidence that naturally
occurring bird vir-ulent strains could be circulating within
theMiddle East and were introduced into NorthAmerica [95].
1.4. Disease and distribution
Clinical disease in humans ranges from mildfever to the
development of severe neurologicaldisease [143]; however,
retrospective serologicalstudies have indicated that the majority
ofWNVinfections are actually asymptomatic [6, 154].West Nile fever
is the most common clinicalmanifestation and is characterized by
the devel-opment of high fever, chills, rash, headache,myalgia and
nausea. Symptoms typically abatewithin 35 days of onset and result
in lifetimeimmunity. WNV infection also may result in
Figure 1. Genomic organization of the WNV genome. Three
structural proteins (C, prM, E) and sevennonstructural proteins
(NS1, 2A, 2B, 3, 4A, 4B and 5) are translated as a single
polyprotein directly fromthe 11 Kb positive-sense RNA genome.
Factors impacting West Nile virus circulation Vet. Res. (2009)
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the development of severe neurological symp-toms that include
encephalitis, meningitis, mye-litis or combinations of these
symptoms [58, 98].Acute flaccid paralysis of the limbs and
respira-tory muscles has been described in North Amer-ica [8] and
Romania [28].
Elderly individuals are at a greater risk fordeveloping severe
neurological disease, withyounger patients more commonly
developingWN fever [106]. It is not readily clear whetherthe more
severe neurological symptoms are theresult of increased virulence
of the introducedstrain or a reflection on the immunologicallynave
status of the population whose age struc-ture might be more
predisposed to severe dis-ease manifestations. Postulated
mechanisms ofviral entry to the CNS and subsequent develop-ment of
more severe disease include impairedstructural elements of the
blood-brain barrier(BBB) or impaired immunity with increasedage
[143]; however, data generated with micro-vascular endothelial
cells indicates the mainte-nance of BBB integrity following
infectionwith WNV, indicating the potential of free virusto pass
this barrier. Furthermore, increased celladhesion molecule
expression observed in thisstudy indicated the potential for
infectedimmune cells to also traverse the BBB [158].
West Nile virus has been found to be ende-mic to Europe [80],
Africa [45, 101], Asiaand Australasia [69]. Within its
geographicrange, outbreaks of febrile disease in humanshave
occurred sporadically with well docu-mented outbreaks being
reported in Egypt[149], France [64] and South Africa [68]
withoutbreaks occurring in 2008 in Romania[116], Hungary [84] and
Italy [93, 133]. Likein the USA [4, 5, 7], recent disease
outbreaksoccurring in Romania [154], Italy [10, 104],Russia [92]
and Israel [30] have been associatedwith the severe disease
symptomology. Since itsintroduction to the USA in 1999, a total
of28 975 human cases including 1 124 deaths(through 2008) have been
documented(www.cdc.gov).
West Nile virus has demonstrated a widehost range, infecting,
for example, equines, alli-gators [62], dogs [9], sheep [71],
llamas [86],alpacas [35, 87]; however, few animals consis-tently
demonstrate overt disease. The attack rate
for equines is approximately 5% with an esti-mated 1 in 3 horses
that demonstrate encephali-tis succumbing to the disease [10, 26].
Otherthan birds, some squirrel [51, 60, 78, 111,113], chipmunk
[112] and rabbit species[153], and potentially alligators [79] most
serveas dead-end hosts in which circulating viremiasare not
sufficient for infection of mosquitovectors.
1.5. Transmission of WNV
Since its identification in 1937 from theWest Nile district in
Uganda [142], WNV trans-mission cycles have been extensively
describedin Egypt [149], South Africa [68], Israel [109]and
Pakistan [3, 55, 121]. These maintenancecycles have all included
ornithophilic mosquitospecies and mostly passerine avian hosts(Fig.
2) that maintain sufficient viremias forthe infection of subsequent
mosquitoes. Isola-tions have been made most extensively
frommosquitoes of the genus Culex, not only inEgypt [148] but also
throughout its pandemicdistribution [121]. In South Africa,
althoughisolations have been made from a wide rangeof mosquitoes,
Culex univittatus is the onlymosquito vector that is efficiently
infected attiters that are present in birds infected withWNV. The
role of alternative mosquito popula-tions in viral transmission is
presumably quitelow [66, 67]. In endemic transmission foci
ofAustralia, Culex annulirostris is the major mos-quito vector
[53], while the Culex vishnui com-plex and Culex tritaeniorhynchus
have beenimplicated with transmission in India andPakistan [3,
102]. Evidence of seroconversionsof birds in endemic foci [81, 100,
165] and vire-mia [164] and antibody [22] production follow-ing
experimental inoculation of bird species hasincriminated avian
hosts as the vertebrate reser-voir for WNV throughout its
distribution. Addi-tionally, certain mammalian species have
beenfound to, in some cases, develop sufficient vire-mia for
infection of mosquito vectors [112, 113,132]; however, the role
that these hosts play inthe transmission dynamics of WNV are
cur-rently uncertain but of significant interest dueto the
potential infection of mammalophagicmosquito vectors.
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Bird mortality has been a unique epidemio-logical finding for
WNV transmission in Israel[19] and North America [131], having
neverbefore been reported during outbreaks of WNfever in Europe
[134] the Middle East [105]or with endemic transmission in
Australia [53]or South Africa [68] (Fig. 2). In contrastto Old
World transmission, isolations of WNVhave been made from numerous
species ofNorth American mosquitoes representing 11genera.
Mosquitoes most commonly infectedin the eastern USA have been
members of theCulex pipiens species complex, and this
speciescomplex was also associated withtransmission during a human
urban epidemic
in Romania in 1996 [154]. However, isolationshave been made from
marginally competentvectors such as the catholic vectors Aedes
albo-pictus and Aedes vexans [155].
In North America, West Nile virus rapidlyexpanded its geographic
range from four statesin 1999 to all contiguous 48 and Canada
by2004 [120]. With this westward transition,WNV has adopted Culex
tarsalis as its predom-inant rural vector in western North
America.The mechanism for viral dispersal has not
beenexperimentally addressed; however, the extre-mely high viremia
titers present within both res-ident and migratory bird species
(> 150)indicate the probable role of some of these bird
Figure 2. Transmission cycles of WNV. Transmission occurs
between ornithophilic mosquito species (Culexspp.) and passeriform
avian hosts. Birds typically manifest high viremias capable of
exceeding oral infectionthresholds for many mosquito vectors.
Humans and equines fail to generate sufficient viremia for
theinfection of mosquito hosts and are deemed dead end or
tangential hosts. Red: Avian mortality was firstidentified in a
migratory stork and subsequently in commercially farmed geese in
the late 1990s and hassubsequently been associated with widespread
mortality among numerous North American avian species
(inparticular, corvids). (A color version of this figure is
available at www.vetres.org.)
Factors impacting West Nile virus circulation Vet. Res. (2009)
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taxa in viral dissemination [131] with the poten-tial for
limited local dispersal by mosquitoes[118].
1.6. Use of crow mortality to trackWNV activity
Deaths in American crow (AMCR) wereespecially prevalent in New
York City in1999 [4] and monitoring of crow mortalityhas been
adopted as an epidemiological indica-tor for the tracking of WNV
transmission in theUSA and has proven useful in predictingincreased
risk for human infections [39, 40,65]. Dead crows with confirmed
WNV infec-tions preceded the first human cases by threemonths in
New York in 2000. Despite this fact,there is no knowledge regarding
the geneticand/or pathological mechanism(s) of suscepti-bility for
WNV in crows or any other birdspecies.
1.7. Virulence and immunity studies with WNV
West Nile virus neurovirulence has beenstudied in primate [114]
as well as mouse [13,52, 160] and hamster models [166].
Age-relatedresistance to neuroinvasion is typical of
mos-quito-borne flaviviruses [42, 48]; however,intraperitoneal
infection of 1516 week-oldmice and adult hamsters with the newly
intro-duced North American genotype induces fatalencephalitis [13].
This finding is in contrast toa study in which WNV encephalitis was
rarein mice older than 7 weeks of age followinginoculation with a
WNV strain from Egypt[160]. Genetic mapping studies have
indicatedthe importance of the IFN-inducible 20-50-oli-goadenylate
synthetase genes with resistanceto WNV infection [99].
Development of encephalitis is identified ator near the time of
clearance of virus from theperipheral circulation concurrent with
the pro-duction of neutralizing antibody in a hamstermodel of WNV
encephalitis. This model hasalso demonstrated that hematogenous
spreadof the virus across the blood-brain barrier isthe most likely
route of entry to the brain asthe olfactory ganglia were not
reported to havebecome infected [166]. Intranasal inoculation
is
a highly inefficient mode of inducing neurovi-rulence in mice,
further indicating that infectionof the olfactory bulb is likely
not the most effi-cient mechanism of viral entry to the brain
[13,52, 110]. Inoculation of mice with differentWNV strains has
demonstrated a correlationbetween viral genotype and
neurotropism[13]; however, genotypes with increased neu-rotropism
do not correlate with increased bind-ing to either human or mouse
brain receptorpreparations [12, 107]. Unlike AMCR that
havegenerated titers of up to 10 log10 PFU/mLserum and uniformly
succumb to infectionwithin 5 days of infection [83], hamstershave
peak viremias of approximately 5 log10TCID50/mL of serum, have
approximately50% survival rates and typically die 714 daysafter
infection with the NY99 WNV genotype[166]. Antibody development may
play animportant role in protecting hamsters frompotentially fatal
encephalitis, since peripheralviral titers dissipate as circulating
neutralizingantibody is produced [151, 166]. Immunizationof
hamsters with heterologous flaviviruses suchas Japanese
encephalitis and St. Louis encepha-litis viruses has demonstrated a
protective effectagainst lethal encephalitis [152].
Administrationof anti-flaviviral antibodies within 46
dayspost-infection has also been demonstrated tobe efficacious for
preventing flaviviral encepha-litis in a mouse model [130]. This
time framecorrelates with viral invasion of neural tissues[52, 130,
166]. Intraperitoneal inoculation ofWNV in a hamster model also
demonstratesthat serum neutralizing antibody developmentwithin five
days of inoculation correlates withdecreased peripheral viral
circulation [166].
2. FACTORS ASSOCIATED WITHWEST NILE VIRAL EMERGENCE
2.1. Virological factors associatedwith emergence
2.1.1. Emergence of avian virulence
An Egyptian strain, Ar-248, was isolatedfrom a moribund pigeon
(Columba livia) squabin a field study conducted from 1952-1954.
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This strain produced morbidity and mortality inexperimentally
infected hooded crows (Corvuscorone) and house sparrows (Passer
domesti-cus) [164]. High seroprevalence rates withinhooded crow
populations in Egypt coupled withthe rapid deaths of the
experimentally inocu-lated bird (some within 1 to 2 days of
infec-tion), indicate the possibility that mortalitycould have been
the result of experimentalhandling of the birds rather than natural
viru-lence from infection [149].
No reports of natural WNV-associated mor-tality in adult birds
occurred during the first sixdecades since the discovery of the
virus in 1937[57]. However, significant avian morbidity
andmortality have been recent hallmarks of WNVoutbreaks in Israel
[19, 147] and North America[17]. In 1998, WNV was identified in
tissuestaken from dead migratory storks in Israel[97] and later
that year, an outbreak withingoose farms across Israel was
identified.Affected flocks had severe mortality rates ingoslings
between 3 and 8 weeks of age [96].Experimental infection of
goslings with viruseslater isolated from North America
demonstratedsimilar mortality and resulted in viremias thatwere
sufficient to infect mosquito vectors[147]. Evaluation of the
virulence of WNV iso-lated from New York in 1999
demonstratedmortality in 8 of 25 species experimentallyinfected.
The most susceptible species werethe blue jay (Cyanocitta
cristata), commongrackle (Quiscalus quiscula), house
finch(Carpodacus mexicanus), AMCR (Corvusbrachyrhynchos), and house
sparrow (Passerdomesticus). Corvids (including AMCR, bluejays
andmagpies) all developed circulating vire-mias in excess of 8
log10 PFU/mL blood and insome cases exceeded 10 log10 PFU/mL
blood[83]. Necropsy tissues taken from naturally[145] and
experimentally infected [83] AMCRhave demonstrated that the North
AmericanWNV is not limited to infection of particularorgan systems,
with virus being identified inthe brain, heart, kidney, lungs,
gonads, spleen,liver, intestines, esophagus and skin.
High mortality rates in AMCR and the quan-tity of virus
identified in various organs havebeen factors for the adoption of
crow mortalityas a surveillance tool to identify areas with
recent WNV activity [39, 40]. WNV infectionwith the NY99
genotype has been identifiedin more than 150 species of birds
representingover 20 bird families in North America,
causingmorbidity in some cases but not necessarilymortality [82,
83, 136]. Chickens, for example,demonstrate no mortality following
infec-tion with WNV, yet titers as high as 5 log10PFU/mL of serum
have been identified andvirus can be isolated from myocardium,
spleen,kidney, lung, and intestine. Additionally,
histo-pathological examination has identified myo-cardial necrosis,
nephritis, and pneumonitismost notably in young birds [136].
The genetic changes observed in differentWNV strains can
modulate their virulencepotential in avian species [23, 91].
Kunjinviruses have demonstrated low peak viremiathresholds compared
to alternative lineage 1WNV strains in both AMCR [23] and HOSP[91].
Other lineage 1 WNV, closely related tobut different from the
highly avian virulentNY99 WNV strain, have also demonstratedreduced
viremia and subsequently loweredmortality rates in AMCR following
experimen-tal infection [77]. These data in accordance withthe
finding that WNV strains circulating inIsrael that are genetically
most similar to theNY99 strain have been associated with
avianvirulence [19] indicate that viral genetics playa crucial role
in host susceptibility to lethalinfection.
2.1.2. Genotype associated with avian virulence
Positive selection modeling of WNV repre-senting members of all
of the lineages has identi-fied a single genetic loci (NS3-249) to
be underadaptive evolution [24]. This residue lies withinthe
helicase domain of theNS3 protein in an areanot associated
directlywithRNAbindingorATPhydrolysis; however, incorporation of a
NY99substitution (NS3-T249P) into a closely relatedlineage 1 WNV
that elicited a low level of viru-lence in AMCR was sufficient to
elicit a viremiaand mortality response in crows indistin-guishable
from the NY99 strain. Interestingly,this avian virulence mutation,
NS3-249P, hasemerged on at least three independent occasions(Fig.
3). In each case, the viruses with this
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substitutionhavebeenassociatedwithhumandis-ease outbreaks;
however, only the Egyptian 1951isolate [164] as well as viruses
from the Israeli/NorthAmerican clades [89] have been associatedwith
avian virulence. The preponderance of thesedata indicated the
potential importance of avianviremia for the emergence of lineage I
WNVand suggests the potential for the emergence ofalternative WNV
genotypes following smallgenetic changes. Interestingly, several
WNVlineages contain the NS3-249P substitution buthave not been
associated with avian virulence or
the emergence of disease outbreaks indicatingthe possible
limitations that particular WNVgenetic backbones could impose on
emergencepotential of alternative genotypes as well as thepotential
role of the NS3-249P for increased rep-lication in a wider array of
avian species.
2.1.3. Increased virulence as a factorfor increased
transmission
A number of avian species are highlysusceptible to WNV
infection, exhibiting high
Figure 3. Maximum likelihood phylogenetic tree of 21 complete
genomes of WNV. Viruses are groupedaccording to four described
lineages ofWNV (excluding the lineage 5 Indian group) and the
genetic residue ateach NS3-249 site is indicated. The three
independent emergences of the NS3-249P genotype has beendenoted on
the tree. In each case an NS3-249Pro genotype emerged (designated
in bold black) from apredecessor genotype (Thr; designated in
grey). The asterisks represent nodes with bootstrap support
values> 95%.
Vet. Res. (2009) 40:43 A.C. Brault
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viremias and associated mortality rates, anddecreases in
abundance [88]. Although it couldbe concluded that this resultant
reduction of thebreeding population would diminish transmis-sion,
high avian mortality is postulated topotentially increase
transmission in three ways:(i) survival of previously infected and
nowimmune birds could dilute the effect of subse-quent transmission
events [50], (ii) mortalityin birds is associated with high
peripheral vire-mia leading to the efficient infection of
moder-ately susceptible mosquito vectors [23, 77, 83],and (iii)
increased pathological manifestationscould favor increased
infection of mosquitoesdue to reduced anti-mosquito defensive
behav-ior of moribund avian hosts [33] as well asincreased
attractiveness to mosquitoes as aresult of hyperthermia [77]. The
time periodinwhich avian hosts such as AMCR are themostviremic
coincides with maximal viremia andmoribund birds, presenting with
elevated vire-mias on the ground could result in
increasedefficiency for infectivity of contact with
vectormosquitoes, thereby increasing transmissionpotential of WNV
to humans or equines [108].Furthermore, it has been hypothesized
that vec-tor-borne agents have the potential for toleranceof higher
levels of mortality. This has been theo-rized to result from
theneed for disseminated rep-lication for the infection of
arthropod vectors thatoften results in more serious clinical
manifesta-tionswithin the vertebrate host. The transmissionof
vector-borne viruses by mobile vectors hasalso been postulated to
compensate for anydampening of transmission due to the lack
ofmobility of moribund vertebrate hosts [34, 43].
In contrast to WNV transmission in NorthAmerica in which low
oral infection rates ofCulex spp. vectors are likely offset by high
vire-mias in avian hosts, limited avian mortality andlow oral
infection thresholds of Cx. univittatusand Cx. tritaeniorhynchus
vectors are transmis-sion hallmarks within endemic foci. Although
afew studies have demonstrated geographic dif-ferences in
susceptibility of Old World endemicmosquito populations [2, 56],
vector compe-tence experiments with North American mos-quitoes have
indicated considerable temporaland spatial variability for oral
susceptibilitywith no discernable pattern that could be linked
to amplification [125]. These data takentogether indicate the
importance of avian ampli-fication by invasive WNV for infection of
mar-ginally susceptible North American Culex spp.while low oral
infection thresholds of specificvectors can allow for transmission
in theabsence of high avian viremias within endemictransmission.
These differing evolutionary strat-egies are also evident with a
closely relatedflavivirus, SLEV. Comparatively, despite thefact
that they utilize the same avian hosts andmosquito vectors, SLEV
has an approximately10-fold greater oral susceptibility than WNVbut
produces low magnitude viremias and isless virulent in birds
[122].
2.1.4. Viral adaptation for replicationat higher temperature
One factor that has classically defined thelimit of the host
range utilized by an RNA virushas been its ability to replicate at
elevated tem-perature [36, 61]. Arboviruses such as WNVhave a wide
range of temperatures in whichthey must replicate in order to be
propagatedwithin both vertebrate and invertebrate hosts.An
arbovirus such as dengue that replicates inprimates is incapable of
replicating at tempera-tures above 39 C. This could be an
importantfactor in the inability of these viruses to utilizebirds
(that have higher body temperatures) asvertebrate hosts [85]. Much
of our knowledgein reference to replication at alternative
temper-atures is the result of the generation of temper-ature
sensitive (ts) viral mutants for theidentification of the
functional role of viral pro-teins in the replication process [140]
or thedevelopment of mutants that have impaired rep-lication
capacity [20, 167] for the developmentof vaccines. Replication of
arboviruses in a twohost system can moderate the amount of
selec-tion that can take place in either the vertebrateor
invertebrate host [159]. Evidence also sug-gests that in vitro
selection for increased repli-cation in vertebrates can result in a
decreasedability to replicate in mosquito tissues [54].The
temperature spectrum for which differentarboviruses can replicate
(and subsequentlythe hosts that they are capable of utilizing)
ispoorly understood.
Factors impacting West Nile virus circulation Vet. Res. (2009)
40:43
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-
Previous studies have defined the potentialimportance of both
temperature constraintswithin avian hosts [77] as well as mosquito
vec-tors for WNV transmission. Degree-day modelshave identified the
replication limit of WNV inmosquito vector to be constrained by
tempera-tures below 14 C and further demonstratedthat the strain of
WNV introduced to NorthAmerican requires warmer temperatures for
dis-semination and subsequent transmission [124]than a WNV strains
from sub-Saharan Africa[31]. Further data has demonstrated that
thegenotype of WNV that has predominated inNorth America since
2002, the WN02 geno-type, seems to disseminate more rapidly andat a
more efficient level at elevated temperaturesthan the prototype
NY99 North American strain[75, 103]. This shortening of the
extrinsic incu-bation period (EIP), the time between a mos-quito
imbibing an infectious bloodmeal andbeing capable of transmitting
virus by bite,could have been the factor by which this geno-type of
virus has been selected. Analyses oftemperature patterns in the USA
have demon-strated an association between above-normaltemperatures
and epidemics of WNV in north-ern latitudes [124]. These data
coupled withthe finding of increased efficiency of vector
dis-semination at elevated temperatures of the pre-dominant WNV
genotype indicate temperatureas a potential important selection
criterion forWNV evolution.
2.2. Environmental factors associatedwith emergence
2.2.1. Climate perturbation
Climate change can have a direct effect onWNV amplification
rates in poikilothermicmosquito vectors as external temperature
hasbeen documented to have an inverse relation-ship to the duration
of the EIP [124]. Addition-ally, increases in transmission season
can resultas well as expansion of transmission to moreextreme
latitudes and elevations. Althoughincreasing temperature is
negatively correlatedwith longevity of mosquitoes, in most
instancesthe increased dissemination and transmissionrates actually
result in increased transmission
efficiency. Patterns of WNV transmission aresignificantly linked
to the abundance of vectorpopulations. It has been determined that
heavyrainfall in the spring and warm, dry tempera-tures during the
summer are optimal for Culexspp. population increases and are
positively cor-related with WNV transmission [120, 126,
137,138].
2.2.2. Species diversity, species behaviorand transmission
dynamics
One explanation for the lack of WNV-associated disease in Latin
America is theincreased avian species diversity in the tropics.It
is hypothesized that increased species diver-sity could negatively
impact transmission ofWNV if there was a high proportion of
incom-petent hosts. One study has made such a con-nection by
identifying a negative correlationbetween non-passerine species
diversity andthe force of WNV transmission, presumablyowing to a
dilution effect of vertebrate hostswith incompetent non-passerine
avian species[44]. Other studies have suggested the impor-tance of
super-spreaders or certain avian spe-cies such as the American
robin (Turdusmigratorius) in temperate habitats that appearto not
only be highly susceptible to infectionwith WNV but also are
preferential sourcesfor bloodmeals [73]. These concepts willrequire
further investigation as a number ofcompeting theories for the
reduced impact ofWNV in Latin America have been proposedincluding
the circulation of WNV strains withreduced virulence phenotypes
[15] and thepotential inhibitory role of acquired immunityto
heterologous flavivirus circulation inMexico, Central and South
America [47].
Shifts in mosquito host selection have beendocumented and
associated with the potentialfor increased infection. One study
indicated thatCulex pipiens mosquitoes in the northeasternUSA shift
their feeding behavior from highlycompetent American robins to
mammals andhumans in the late summer to early fall, coin-ciding
with the emigration of this avian species[74]. This host switching
has also beenobserved with Culex tarsalis in the westernUSA [150]
and Cx. nigripalpus in Florida
Vet. Res. (2009) 40:43 A.C. Brault
Page 10 of 19 (page number not for citation purpose)
-
[38], indicating the importance of feedingbehavior in the
tangential transmission ofWNV. Utilizing microsatellite markers to
genet-ically distinguish Nearctic and Palearctic Culexspp.
mosquitoes, one study inferred thatPalearctic European species
limit their feedingto avian hosts while North American
Nearcticspecies feed indiscriminately upon avian andmammalian hosts
[49] and concluded that thisdifferential feeding behavior was the
explana-tion for the lack of persistent WNV activity inEurope.
However, a number of other studies[144] have provided evidence that
PalearcticEuropean Culex spp. feed on both mammalianand avian
hosts, which contradicts the conclu-sion that feeding behavior
could modulate epi-demiological patterns.
Previously, WNV infection in AMCR hasbeen uniformly lethal.
However, the detectionof seropositive AMCR has been reported,
indi-cating that survival of individual birds in thesehighly
susceptible avian species can occur[163]. Resistance to lethal
infection could beassociated with lower peak viremia, thus lead-ing
to selection for WNV genotypes withreduced oral infective
thresholds for mosqui-toes. As such, the effect that these
modulationsin vertebrate host population susceptibilitycould have
on a concomitant selection forincreased oral susceptibility of
mosquito vectorsshould be monitored closely.
2.2.3. Role of heterologous flaviviruses on WNVtransmission
The effect that the presence of heterologousflaviviruses has had
on WNV transmission is asubject of some debate; however, it is
apparentthat increased avian herd immunity and mortal-ity has had a
detrimental effect on the transmis-sion of, for instance, SLEV in
southwesterntransmission foci [127]. Cross-protection withWNV has
been demonstrated to precludeHouse finches (HOFI) from mounting
detect-able viremia following SLEV challenge. Con-versely,
inoculation of HOFI with SLEV priorto WNV infection substantially
reduces WNVviremia to levels below that associated with
oralinfection in most mosquito vectors [46, 123].The potential
effect of selective pressures from
heterologous flaviviral immunity is currentlynot known.
Heterologous infection of vertebratehosts and mosquito vectors with
alternative fla-viviruses could also result in potential
recombi-nation events as well as block mosquitoinfectivity through
barriers to super-infection.Barriers to super-infection have been
describedpreviously for arthropod-borne viruses [16, 32,37, 41, 70,
141, 146]. For example, Aedes tri-seriatus mosquitoes
experimentally infectedwith LaCrosse virus (LACV) have been shownto
be resistant to infection with another closelyrelated bunyavirus,
Snowshoe Hare virus(SSHV), approximately two days
post-infection[16]. A resistance period for dual infection
wasidentified for ticks co-infected with Thogotovirus (THOV) for a
period ranging between24 h and 10 days of the initial infection
withan alternative THOV strain [32]. An Aedes alb-opictus cell
(C6/36) model further demonstratedthat the inhibition of the
secondarily infectingalphavirus is sequence specific. Alternative
al-phaviruses were blocked from super-infectionof C6/36 cells,
while unrelated bunyavirus orflaviviruses could establish infection
in alphavi-ruses-infected C6/36 cells within the time per-iod that
these cells were resistant to infectionwith heterologous
alphaviruses [37, 70]. Themechanism for this super-infection
exclusionhas not been identified; however, it has beenhypothesized
that competitive exclusionthrough template scavenging during RNA
repli-cation as well incompatible interactionsbetween viral
proteins exclude replication ofthe secondarily infecting virus.
Inhibitoryeffects on the super-infecting virus have beenidentified
in the processes of binding to the cel-lular surface receptors, low
pH fusion with theendocytic vesicle, viral uncoating, viral
replica-tion as well as viral maturation and budding[141].
2.2.4. Alternation of transmission patterns
Since WNV was introduced into the USA in1999, an identified
pattern has been recognizedin which the season of introduction is
character-ized by mild activity with few human cases.This is
followed by an epidemic year character-ized by large numbers of
cases, high infection
Factors impacting West Nile virus circulation Vet. Res. (2009)
40:43
(page number not for citation purpose) Page 11 of 19
-
rates in mosquitoes with subsequent avian sero-conversions and
mortality. The third season ofactivity has been referred to as the
subsidenceyear in which human cases and enzootic indi-cators drop
precipitously, presumably owing toincreased herd immunity and avian
depopula-tion of highly competent amplification hosts[119].
Decreased avian herd immunity resultingfrom the presence of nave
hatchlings as well aswaning immunity in after-hatch year birds
isthen conducive for continued transmission dur-ing subsequent
seasons. In contrast, areas lack-ing super spreaders or highly
susceptiblecorvids have failed to amplify enzootic trans-mission to
outbreak levels [127], whereas otherareas have experienced
recurring epidemic leveltransmission during sequential seasons
[128].The identification of more severe neurologicalsyndromes in
North America could be the resultof an increased virulence of the
WNV strainintroduced as well as age-related exposure ratesin a
completely nave population. Within ende-mic areas of WNV or SLEV
transmission inwhich youth exposure rates are high, neuroin-vasive
disease is uncommon. While the viru-lence of the imported strains
deserves furtherattention, the role of a virgin soil effectshould
not be overlooked as an explanationfor the altered disease
phenotypes observed inNorth America.
3. CONCLUSION
Since its introduction to North America,WNV has undergone a
dramatic increase ingeographic range and has demonstrated agreater
association with a more severe neuro-logical clinical presentation.
Undoubtedly anumber of ecological, virological and socialfactors
have contributed to this emergence.Virological factors highlighted
in this reviewhave included genetic adaptation for
increasedreplication in avian hosts as well as
increaseddissemination in mosquito vectors at elevatedtemperatures.
As with other RNA viruses, thepresence of an error-prone polymerase
thatlacks proofreading function coupled with thelarge population
sizes occurring in both infectedavian hosts and mosquito vectors
allow for the
rapid selection of novel genotypes. Novel eco-logical niches
that have been created by cli-matic perturbations and social or
demographicchanges assuredly will result in the emergenceof novel
genotypes to occupy these habitatsand thus perpetuate the
continually changinglandscape of WNV epidemiology.
Acknowledgements. I would like to thank Dr EddieHolmes for the
construction of the Phylogenetic treepresented in Figure 3 as well
as Dr Bill Reisen forhis many helpful suggestions.
REFERENCES
[1] Adams S.C., Broom A.K., Sammels L.M.,Hartnett A.C., Howard
M.J., Coelen R.J., et al.,Glycosylation and antigenic variation
among Kunjinvirus isolates, Virology (1995) 206:4956.
[2] Ahmed T., Hayes C.G., Baqar S., Comparison ofvector
competence for West Nile virus of colonizedpopulations of Culex
tritaeniorhynchus from southernAsia and the Far East, Southeast
Asian J. Trop. Med.Public Health (1979) 10:498504.
[3] Akhter R., Hayes C.G., Baqar S., Reisen W.K.,West Nile virus
in Pakistan III. Comparative vectorcapability of Culex
tritaeniorhynchus and eight otherspecies of mosquitoes, Trans. R.
Soc. Trop. Med. Hyg.(1982) 76:449453.
[4] Anonymous, Outbreak of West Nile-like viralencephalitis New
York, 1999, MMWR Morb.Mortal. Wkly Rep. (1999) 48:845849.
[5] Anonymous, Update: West Nile-like viral enceph-alitis New
York, 1999, MMWR Morb. Mortal. WklyRep. (1999) 48:890892.
[6] Anonymous, Human West Nile virus surveillance Connecticut,
New Jersey, and New York, 2000,MMWR Morb. Mortal. Wkly Rep. (2001)
50:265268.
[7] Anonymous, West Nile virus infection may begreater than
previously thought, FDA Consum. (2001)35:38.
[8] Anonymous, Acute flaccid paralysis syndromeassociated with
West Nile virus infection - Mississippiand Louisiana, JulyAugust
2002, MMWR Morb.Mortal. Wkly Rep. (2002) 51:825828.
[9] Austgen L.E., Bowen R.A., Bunning M.L.,Davis B.S., Mitchell
C.J., Chang G.J., Experimentalinfection of cats and dogs with West
Nile virus,Emerg. Infect. Dis. (2004) 10:8286.
Vet. Res. (2009) 40:43 A.C. Brault
Page 12 of 19 (page number not for citation purpose)
-
[10] Autorino G.L., Battisti A., Deubel V., Ferrari G.,Forletta
R., Giovannini A., et al., West Nile virusepidemic in horses,
Tuscany region, Italy, Emerg.Infect. Dis. (2002) 8:13721378.
[11] Bakonyi T., Hubalek Z., Rudolf I., Nowotny N.,Novel
flavivirus or new lineage of West Nile viruscentral Europe, Emerg.
Infect. Dis. (2005) 11:225231.
[12] Beasley D.W., Li L., Suderman M.T., BarrettA.D., West Nile
virus strains differ in mouse neuro-virulence and binding to mouse
or human brainmembrane receptor preparations, Ann. N.Y. Acad.Sci.
(2001) 951:332335.
[13] Beasley D.W., Li L., Suderman M.T., BarrettA.D., Mouse
neuroinvasive phenotype of West Nilevirus strains varies depending
upon virus genotype,Virology (2002) 296:1723.
[14] Beasley D.W., Davis C.T., Guzman H.,Vanlandingham D.L.,
Travassos da Rosa A.P., ParsonsR.E., et al., Limited evolution of
West Nile virus hasoccurred during its southwesterly spread in the
UnitedStates, Virology (2003) 309:190195.
[15] Beasley D.W., Davis C.T., Estrada-Franco J.,Navarro-Lopez
R., Campomanes-Cortes A., TeshR.B., et al., Genome sequence and
attenuating muta-tions in West Nile virus isolate from Mexico,
Emerg.Infect. Dis. (2004) 10:22212224.
[16] Beaty B.J., Sundin D.R., Chandler L.J., BishopD.H.,
Evolution of bunyaviruses by genome reassort-ment in dually
infected mosquitoes (Aedes triseriatus),Science (1985)
230:548550.
[17] Bernard K.A., Maffei J.G., Jones S.A.,Kauffman E.B., Ebel
G., Dupuis A.P. 2nd, et al.,West Nile virus infection in birds and
mosquitoes,New York State, 2000, Emerg. Infect. Dis.
(2001)7:679685.
[18] Berthet F.X., Zeller H.G., Drouet M.T.,Rauzier J., Digoutte
J.P., Deubel V., Extensive nucle-otide changes and deletions within
the envelopeglycoprotein gene of Euro-African West Nile viruses,J.
Gen. Virol. (1997) 78:22932297.
[19] Bin H., Grossman Z., Pokamunski S., MalkinsonM., Weiss L.,
Duvdevani P., et al., West Nile fever inIsrael 19992000: from geese
to humans, Ann. N.Y.Acad. Sci. (2001) 951:127142.
[20] Blaney J.E. Jr., Manipon G.G., Murphy B.R.,Whitehead S.S.,
Temperature sensitive mutations inthe genes encoding the NS1, NS2A,
NS3, and NS5nonstructural proteins of dengue virus type 4
restrictreplication in the brains of mice, Arch. Virol.
(2003)148:9991006.
[21] Bondre V.P., Jadi R.S., Mishra A.C., YergolkarP.N.,
Arankalle V.A., West Nile virus isolates from
India: evidence for a distinct genetic lineage, J. Gen.Virol.
(2007) 88:875884.
[22] Boyle D.B., Marshall I.D., Dickerman R.W.,Primary antibody
responses of herons to experimentalinfection with Murray Valley
encephalitis and Kunjinviruses, Aust. J. Exp. Biol. Med. Sci.
(1983) 61:665674.
[23] Brault A.C., Langevin S.A., Bowen R.A.,Panella N.A.,
Biggerstaff B.J., Miller B.R., KomarN., Differential virulence of
West Nile strains forAmerican crows, Emerg. Infect. Dis. (2004)
10:21612168.
[24] Brault A.C., Huang C.Y., Langevin S.A., KinneyR.M., Bowen
R.A., Ramey W.N., et al., A singlepositively selected West Nile
viral mutation confersincreased virogenesis in American crows, Nat.
Genet.(2007) 39:11621166.
[25] Brinton M.A., Dispoto J.H., Sequence andsecondary structure
analysis of the 50-terminal regionof flavivirus genome RNA,
Virology (1988) 162:290299.
[26] Bunning M.L., Bowen R.A., Cropp B., SullivanK., Davis B.,
Komar N., et al., Experimental infectionof horses with West Nile
virus and their potential toinfect mosquitoes and serve as
amplifying hosts, Ann.N.Y. Acad. Sci. (2001) 951:338339.
[27] Calisher C.H., Karabatsos N., Dalrymple J.M.,Shope R.E.,
Porterfield J.S., Westaway E.G., BrandtW.E., Antigenic
relationships between flaviviruses asdetermined by
cross-neutralization tests with poly-clonal antisera, J. Gen.
Virol. (1989) 70:3743.
[28] Ceausu E., Erscoiu S., Calistru P., Ispas D.,Dorobat O.,
Homos M., et al., Clinical manifestationsin the West Nile virus
outbreak, Rom. J. Virol. (1997)48:311.
[29] Charrel R.N., Brault A.C., Gallian P., LemassonJ.J., Murgue
B., Murri S., et al., Evolutionaryrelationship between Old World
West Nile virusstrains. Evidence for viral gene flow between
Africa,the Middle East, and Europe, Virology (2003)315:381388.
[30] Chowers M.Y., Lang R., Nassar F., Ben-DavidD., Giladi M.,
Rubinshtein E., et al., Clinical charac-teristics of the West Nile
fever outbreak, Israel, 2000,Emerg. Infect. Dis. (2001)
7:675678.
[31] Cornel A.J., Jupp P.G., Blackburn N.K., Envi-ronmental
temperature on the vector competence ofCulex univittatus (Diptera:
Culicidae) for West Nilevirus, J. Med. Entomol. (1993)
30:449456.
[32] Davies C.R., Jones L.D., Nuttall P.A., Viralinterference in
the tick, Rhipicephalus appendiculatus.
Factors impacting West Nile virus circulation Vet. Res. (2009)
40:43
(page number not for citation purpose) Page 13 of 19
-
I. Interference to oral superinfection by Thogoto virus,J. Gen.
Virol. (1989) 70:24612468.
[33] Day J.F., Edman J.D., Malaria renders micesusceptible to
mosquito feeding when gametocytes aremost infective, J. Parasitol.
(1983) 69:163170.
[34] Day T., Parasite transmission modes and theevolution of
virulence, Evolution (2001) 55:23892400.
[35] Dunkel B., Del Piero F., Wotman K.L., JohnsI.C., Beech J.,
Wilkins P.A., Encephalomyelitis fromWest Nile flavivirus in 3
alpacas, J. Vet. Intern. Med.(2004) 18:365367.
[36] Dunster L.M., Gibson C.A., Stephenson J.R.,Minor P.D.,
Barrett A.D., Attenuation of virulence offlaviviruses following
passage in HeLa cells, J. Gen.Virol. (1990) 71:601607.
[37] Eaton B.T., Heterologous interference in Aedesalbopictus
cells infected with alphaviruses, J. Virol.(1979) 30:4555.
[38] Edman J.D., Taylor D.J., Culex nigripalpus:seasonal shift
in the bird-mammal feeding ratio in amosquito vector of human
encephalitis, Science(1968) 161:6768.
[39] Eidson M., Komar N., Sorhage F., Nelson R.,Talbot T.,
Mostashari F., McLean R., Crow deaths as asentinel surveillance
system for West Nile virus in thenortheastern United States, 1999,
Emerg. Infect. Dis.(2001) 7:615620.
[40] Eidson M., Kramer L., Stone W., Hagiwara Y.,Schmit K., Dead
bird surveillance as an early warningsystem for West Nile virus,
Emerg. Infect. Dis. (2001)7:631635.
[41] el Hussein A., Ramig R.F., Holbrook F.R., BeatyB.J.,
Asynchronous mixed infection of Culicoidesvariipennis with
bluetongue virus serotypes 10 and 17,J. Gen. Virol. (1989)
70:33553362.
[42] Eldadah A.H., Nathanson N., Sarsitis R., Path-ogenesis of
West Nile virus encephalitis in mice andrats. 1. Influence of age
and species on mortality andinfection, Am. J. Epidemiol. (1967)
86:765775.
[43] Ewald P.W., The evolution of virulence andemerging
diseases, J. Urban Health (1998) 75:480491.
[44] Ezenwa V.O., Godsey M.S., King R.J., GuptillS.C., Avian
diversity and West Nile virus: testingassociations between
biodiversity and infectious dis-ease risk, Proc. Biol. Sci. (2006)
273:109117.
[45] Fagbami A., Human arthropod-borne virusinfections in
Nigeria. Serological and virologicalinvestigations and Shaki, Oyo
State, J. Hyg. Epidem-iol. Microbiol. Immunol. (1978)
22:184189.
[46] Fang Y., Reisen W.K., Previous infection withWest Nile or
St. Louis encephalitis viruses providescross protection during
reinfection in house finches,Am. J. Trop. Med. Hyg. (2006)
75:480485.
[47] Farfan-Ale J.A., Lorono-Pino M.A., Garcia-Rejon J.E., Hovav
E., Powers A.M., Lin M., et al.,Detection of RNA from a Novel West
Nile-like virusand high prevalence of an insect-specific flavivirus
inmosquitoes in the Yucatan Peninsula of Mexico, Am.J. Trop. Med.
Hyg. (2009) 80:8595.
[48] Fitzgeorge R., Bradish C.J., The in vivo differ-entiation
of strains of yellow fever virus in mice, J.Gen. Virol. (1980)
46:113.
[49] Fonseca D.M., Keyghobadi N., Malcolm C.A.,Mehmet C.,
Schaffner F., Mogi M., et al., Emergingvectors in the Culex pipiens
complex, Science (2004)303:15351538.
[50] Foppa I.M., Spielman A., Does reservoir hostmortality
enhance transmission of West Nile virus?,Theor. Biol. Med. Model.
(2007) 4:17.
[51] Gomez A., Kramer L.D., Dupuis A.P. 2nd,Kilpatrick A.M.,
Davis L.J., Jones M.J., et al.,Experimental infection of eastern
gray squirrels(Sciurus carolinensis) with West Nile virus, Am.
J.Trop. Med. Hyg. (2008) 79:447451.
[52] Halevy M., Akov Y., Ben-Nathan D., Kobiler D.,Lachmi B.,
Lustig S., Loss of active neuroinvasivenessin attenuated strains of
West Nile virus: pathogenicityin immunocompetent and SCID mice,
Arch. Virol.(1994) 137:355370.
[53] Hall R.A., Broom A.K., Smith D.W., MackenzieJ.S., The
ecology and epidemiology of Kunjin virus,Curr. Top. Microbiol.
Immunol. (2002) 267:253269.
[54] Hanley K.A., Manlucu L.R., Gilmore L.E.,Blaney J.E. Jr.,
Hanson C.T., Murphy B.R., et al., Atrade-off in replication in
mosquito versus mammaliansystems conferred by a point mutation in
the NS4Bprotein of dengue virus type 4, Virology
(2003)312:222232.
[55] Hayes C.G., Baqar S., Ahmed T., ChowdhryM.A., Reisen W.K.,
West Nile virus in Pakistan. 1.Sero-epidemiological studies in
Punjab Province,Trans. R. Soc. Trop. Med. Hyg. (1982)
76:431436.
[56] Hayes C.G., Baker R.H., Baqar S., Ahmed T.,Genetic
variation for West Nile virus susceptibility inCulex
tritaeniorhynchus, Am. J. Trop. Med. Hyg.(1984) 33:715724.
[57] Hayes C.G., West Nile Fever, in: Monath T.P.(Ed.), The
Arboviruses: epidemiology and ecology,CRC Press, Boca Raton, FL,
1988, pp. 5988.
Vet. Res. (2009) 40:43 A.C. Brault
Page 14 of 19 (page number not for citation purpose)
-
[58] Hayes E.B., Virology, pathology, and clinicalmanifestations
of West Nile virus disease, Emerg.Infect. Dis. (2005)
11:11741179.
[59] Heinz F., Collet M., Purcell R., Gould E.,Howeard C.,
Houghton M., Family Flaviviridae, in:Van Regenmortel M. (Ed.),
Virus taxonomy: classifi-cation and nomenclature of viruses,
Academic Press,San Diego, 2000, pp. 859878.
[60] Heinz-Taheny K.M., Andrews J.J., Kinsel M.J.,Pessier A.P.,
Pinkerton M.E., Lemberger K.Y., et al.,West Nile virus infection in
free-ranging squirrels inIllinois, J. Vet. Diagn. Invest. (2004)
16:186190.
[61] Huang C.Y., Butrapet S., Pierro D.J., Chang G.J.,Hunt A.R.,
Bhamarapravati N., et al., Chimericdengue type 2 (vaccine strain
PDK-53)/dengue type1 virus as a potential candidate dengue type 1
virusvaccine, J. Virol. (2000) 74:30203028.
[62] Jacobson E.R., Ginn P.E., Troutman J.M., FarinaL., Stark
L., Klenk K., et al., West Nile virus infectionin farmed American
alligators (Alligator mississippi-ensis) in Florida, J. Wildl. Dis.
(2005) 41:96106.
[63] Jia X.Y., Briese T., Jordan I., Rambaut A., ChiH.C.,
Mackenzie J.S., et al., Genetic analysis of WestNile New York 1999
encephalitis virus, Lancet (1999)354:19711972.
[64] Joubert L., Oudar J., Hannoun C., Beytout D.,Corniou B.,
Guillon J.C., et al., Epidemiology of theWest Nile virus: study of
a focus in Camargue. IV.Meningo-encephalomyelitis of the horse,
Ann. Inst.Pasteur (Paris) (1970) 118:239247 (in French).
[65] Julian K.G., Eidson M., Kipp A.M., Weiss E.,Petersen L.R.,
Miller J.R., et al., Early season crowmortality as a sentinel for
West Nile virus disease inhumans, northeastern United States,
Vector BorneZoonotic Dis. (2002) 2:145155.
[66] Jupp P.G., Laboratory studies on the transmis-sion of West
Nile virus by Culex (Culex) univittatus)Theobald; factors
influencing the transmission rate,J. Med. Entomol. (1974)
11:455458.
[67] Jupp P.G., Laboratory studies on the vectorcapability of
Aedes (neomelaniconion) unidentatusMcIntosh and Aedes (Aedimorphus
dentatus Theo-bald) with West Nile and Sindbis viruses, S. Afr.J.
Med. Sci. (1976) 41:265269.
[68] Jupp P.G., The ecology of West Nile virus inSouth Africa
and the occurrence of outbreaks inhumans, Ann. N.Y. Acad. Sci.
(2001) 951:143152.
[69] Kanamitsu M., Taniguchi K., Urasawa S., OgataT., Wada Y.,
Saroso J.S., Geographic distribution ofarbovirus antibodies in
indigenous human populationsin the Indo-Australian archipelago, Am.
J. Trop. Med.Hyg. (1979) 28:351363.
[70] Karpf A.R., Lenches E., Strauss E.G., StraussJ.H., Brown
D.T., Superinfection exclusion of alpha-viruses in three mosquito
cell lines persistentlyinfected with Sindbis virus, J. Virol.
(1997) 71:71197123.
[71] Kecskemeti S., Bajmocy E., Bacsadi A., Kiss I.,Bakonyi T.,
Encephalitis due to West Nile virus in asheep, Vet. Rec. (2007)
161:568569.
[72] Khromykh A.A., Meka H., Guyatt K.J., West-away E.G.,
Essential role of cyclization sequences inflavivirus RNA
replication, J. Virol. (2001) 75:67196728.
[73] Kilpatrick A.M., Daszak P., Jones M.J., MarraP.P., Kramer
L.D., Host heterogeneity dominates WestNile virus transmission,
Proc. Biol. Sci. (2006) 273:23272333.
[74] Kilpatrick A.M., Kramer L.D., Jones M.J., MarraP.P., Daszak
P., West Nile virus epidemics in NorthAmerica are driven by shifts
in mosquito feedingbehavior, PLoS Biol. (2006) 4:e82.
[75] Kilpatrick A.M., Meola M.A., Moudy R.M.,Kramer L.D.,
Temperature, viral genetics, and thetransmission of West Nile virus
by Culex pipiensmosquitoes, PLoS Pathog. (2008) 4:e1000092.
[76] Kimura T., Ohyama A., Association between thepH-dependent
conformational change of West Nileflavivirus E protein and
virus-mediated membranefusion, J. Gen. Virol. (1988)
69:12471254.
[77] Kinney R.M., Huang C.Y., Whiteman M.C.,Bowen R.A., Langevin
S.A., Miller B.R., Brault A.C.,Avian virulence and thermostable
replication of theNorth American strain of West Nile virus, J.
Gen.Virol. (2006) 87:36113622.
[78] Kiupel M., Simmons H.A., Fitzgerald S.D., WiseA., Sikarskie
J.G., Cooley T.M., et al., West Nile virusinfection in Eastern fox
squirrels (Sciurus niger), Vet.Pathol. (2003) 40:703707.
[79] Klenk K., Snow J., Morgan K., Bowen R.,Stephens M., Foster
F., et al., Alligators as West Nilevirus amplifiers, Emerg. Infect.
Dis. (2004) 10:21502155.
[80] Kolman J.M., Serologic examination of somedomestic animals
from South Moravia on the presenceof antibodies to selected
arboviruses of the A, B,California and Bunyamwera groups, Folia
Parasitol.(1973) 20:353360.
[81] Kolman J.M., Folk C., Hudec K., Reddy G.N.,Serologic
examination of birds from the area ofsouthern Moravia for the
presence of antibodiesagainst arboviruses of the groups Alfa,
Flavo, Uuk-uniemi, Turlock and Bunyamwera supergroup. II.Wild
living birds, Folia Parasitol. (1976) 23:251255.
Factors impacting West Nile virus circulation Vet. Res. (2009)
40:43
(page number not for citation purpose) Page 15 of 19
-
[82] Komar N., Panella N.A., Burns J.E., Dusza S.W.,Mascarenhas
T.M., Talbot T.O., Serologic evidence forWest Nile virus infection
in birds in the New York Cityvicinity during an outbreak in 1999,
Emerg. Infect.Dis. (2001) 7:621625.
[83] Komar N., Langevin S., Hinten S., Nemeth N.,Edwards E.,
Hettler D., et al., Experimental infectionof North American birds
with the New York 1999strain of West Nile virus, Emerg. Infect.
Dis. (2003)9:311322.
[84] Krisztalovics K., Ferenczi E., Molnar Z., CsohanA., Ban E.,
Zoldi V., Kaszas K., West Nile virusinfections in Hungary,
AugustSeptember 2008, EuroSurveill. (2008) 13:19030.
[85] Kuno G., Factors influencing the transmission ofdengue
viruses, in: Gubler D.J., Kuno G. (Eds.),Dengue and dengue
hemorrhagic Fever, CAB Inter-national, New York, 1997, pp.
6188.
[86] Kutzler M.A., Baker R.J., Mattson D.E.,Humoral response to
West Nile virus vaccination inalpacas and llamas, J. Am. Vet. Med.
Assoc. (2004)225:414416.
[87] Kutzler M.A., Bildfell R.J., Gardner-Graff K.K.,Baker R.J.,
Delay J.P., Mattson D.E., West Nile virusinfection in two alpacas,
J. Am. Vet. Med. Assoc.(2004) 225:921924, 880.
[88] Ladeau S.L., Kilpatrick A.M., Marra P.P., WestNile virus
emergence and large-scale declines of NorthAmerican bird
populations, Nature (2007) 447:710713.
[89] Lanciotti R.S., Roehrig J.T., Deubel V., Smith J.,Parker
M., Steele K., et al., Origin of the West Nilevirus responsible for
an outbreak of encephalitis in thenortheastern United States,
Science (1999) 286:23332337.
[90] Lanciotti R.S., Ebel G.D., Deubel V., Kerst A.J.,Murri S.,
Meyer R., et al., Complete genome seq-uences and phylogenetic
analysis of West Nile virusstrains isolated from the United States,
Europe, and theMiddle East, Virology (2002) 298:96105.
[91] Langevin S.A., Brault A.C., Panella N.A.,Bowen R.A., Komar
N., Variation in virulence ofWest Nile virus strains for house
sparrows (Passerdomesticus), Am. J. Trop. Med. Hyg. (2005)
72:99102.
[92] Lvov D.K., Butenko A.M., Gromashevsky V.L.,Kovtunov A.I.,
Prilipov A.G., Kinney R., et al., WestNile virus and other zoonotic
viruses in Russia:examples of emerging-reemerging situations,
Arch.Virol. Suppl. (2004) 8596.
[93] Macini P., Squintani G., Finarelli A.C., AngeliniP.,
Martini E., Tamba M., et al., Detection of West Nile
virus infection in horses, Italy, September 2008, EuroSurveill.
(2008) 13:18990.
[94] Mackenzie J.S., Barrett A.D., Deubel V., TheJapanese
encephalitis serological group of flaviviruses:a brief introduction
to the group, Curr. Top. Microbiol.Immunol. (2002) 267:110.
[95] Malkinson M., Banet C., Weisman J.,Prokamonski S., King R.,
West Nile fever: recentevidence for the intercontinental dispersion
of the virusby migratory birds, Proceedings of the 11th
Interna-tional Congress of Virology, Sydney, Australia,
Inter-national Union of Microbiological Societies, 1999.
[96] Malkinson M., Banet C., Khinich Y., Samina I.,Pokamunski
S., Weisman Y., Use of live and inacti-vated vaccines in the
control of West Nile fever indomestic geese, Ann. N.Y. Acad. Sci.
(2001) 951:255261.
[97] Malkinson M., Weisman Y., Pokamonski S.,King R., Deubel V.,
Intercontinental transmission ofWest Nile virus by migrating white
storks, Emerg.Infect. Dis. (2001) 7:540.
[98] Marfin A.A., Gubler D.J., West Nile encephali-tis: an
emerging disease in the United States, Clin.Infect. Dis. (2001)
33:17131719.
[99] Mashimo T., Lucas M., Simon-Chazottes D.,Frenkiel M.P.,
Montagutelli X., Ceccaldi P.E., et al., Anonsense mutation in the
gene encoding 20-50-oligoa-denylate synthetase/L1 isoform is
associated withWest Nile virus susceptibility in laboratory
mice,Proc. Natl. Acad. Sci. USA (2002) 99:1131111316.
[100] McIntosh B.M., Dickinson D.B., McGillivrayG.M., Ecological
studies on Sindbis and West Nileviruses in South Africa. V. The
response of birds toinoculation of virus, S. Afr. J. Med. Sci.
(1969) 34:7782.
[101] Miller B.R., Nasci R.S., Godsey M.S., SavageH.M., Lutwama
J.J., Lanciotti R.S., Peters C.J., Firstfield evidence for natural
vertical transmission of WestNile virus in Culex univittatus
complex mosquitoesfrom Rift Valley province, Kenya, Am. J. Trop.
Med.Hyg. (2000) 62:240246.
[102] Mishra A.C., Mourya D.T., Transovarial trans-mission of
West Nile virus in Culex vishnui mosquito,Indian J. Med. Res.
(2001) 114:212214.
[103] Moudy R.M., Meola M.A., Morin L.L., EbelG.D., Kramer L.D.,
A newly emergent genotype ofWest Nile virus is transmitted earlier
and moreefficiently by culex mosquitoes, Am. J. Trop. Med.Hyg.
(2007) 77:365370.
[104] Murgue B., Murri S., Triki H., Deubel V., ZellerH.G., West
Nile in the Mediterranean basin: 19502000, Ann. N.Y. Acad. Sci.
(2001) 951:117126.
Vet. Res. (2009) 40:43 A.C. Brault
Page 16 of 19 (page number not for citation purpose)
-
[105] Murgue B., Zeller H., Deubel V., The ecologyand
epidemiology of West Nile virus in Africa Europeand Asia, Curr.
Top. Microbiol. Immunol. (2002)267:195221.
[106] Nash D., Mostashari F., Fine A., Miller J.,OLeary D.,
Murray K., et al., The outbreak of WestNile virus infection in the
New York City area in 1999,N. Engl. J. Med. (2001)
344:18071814.
[107] Ni H., Ryman K.D., Wang H., Saeed M.F., HullR., Wood D.,
et al., Interaction of yellow fever virusFrench neurotropic vaccine
strain with monkey brain:characterization of monkey brain membrane
receptorescape variants, J. Virol. (2000) 74:29032906.
[108] Nielsen C.F., Reisen W.K., West Nile virus-infected dead
corvids increase the risk of infection inCulex mosquitoes (Diptera:
Culicidae) in domesticlandscapes, J. Med. Entomol. (2007)
44:10671073.
[109] Nir Y., Goldwasser R., Lasowski Y., MargalitJ., Isolation
of West Nile virus strains from mosquitoesin Israel, Am. J.
Epidemiol. (1968) 87:496501.
[110] Odelola H.A., Oduye O.O., West Nile virusinfection of
adult mice by oral route, Arch. Virol.(1977) 54:251253.
[111] Padgett K.A., Reisen W.K., Kahl-Purcell N.,Fang Y.,
Cahoon-Young B., Carney R., et al., WestNile virus infection in
tree squirrels (Rodentia:Sciuridae) in California, 20042005, Am. J.
Trop.Med. Hyg. (2007) 76:810813.
[112] Platt K.B., Tucker B.J., Halbur P.G.,Tiawsirisup S.,
Blitvich B.J., Fabiosa F.G., et al.,West Nile virus viremia in
eastern chipmunks (Tamiasstriatus) sufficient for infecting
different mosquitoes,Emerg. Infect. Dis. (2007) 13:831837.
[113] Platt K.B., Tucker B.J., Halbur P.G., BlitvichB.J.,
Fabiosa F.G., Mullin K., et al., Fox squirrels(Sciurus niger)
develop West Nile virus viremiassufficient for infecting select
mosquito species, VectorBorne Zoonotic Dis. (2008) 8:225233.
[114] Pogodina V.V., Frolova M.P., Malenko G.V.,Fokina G.I.,
Koreshkova G.V., Kiseleva L.L., et al.,Study on West Nile virus
persistence in monkeys,Arch. Virol. (1983) 75:7186.
[115] Poidinger M., Hall R.A., Mackenzie J.S.,Molecular
characterization of the Japanese encephali-tis serocomplex of the
flavivirus genus, Virology(1996) 218:417421.
[116] Popovici F., Sarbu A., Nicolae O., Pistol A.,Cucuiu R.,
Stolica B., et al., West Nile fever in apatient in Romania, August
2008: case report, EuroSurveill. (2008) 13:18989.
[117] Prilipov A.G., Kinney R.M., Samokhvalov E.I.,Savage H.M.,
Alkhovskii S.V., Tsuchiya K.R., et al.,Analysis of new variants of
West Nile fever virus,Vopr. Virusol. (2002) 47:3641 (in
Russian).
[118] Rappole J.H., Compton B.W., Leimgruber P.,Robertson J.,
King D.I., Renner S.C., Modelingmovement of West Nile virus in the
Western hemi-sphere, Vector Borne Zoonotic Dis. (2006)
6:128139.
[119] Reisen W., Lothrop H., Chiles R., Madon M.,Cossen C.,
Woods L., et al., West Nile virus inCalifornia, Emerg. Infect. Dis.
(2004) 10:13691378.
[120] Reisen W., Brault A.C., West Nile virus inNorth America:
perspectives on epidemiology andintervention, Pest. Manage. Sci.
(2007) 63:641646.
[121] Reisen W.K., Hayes C.G., Azra K., Niaz S.,Mahmood F.,
Parveen T., et al., West Nile virus inPakistan, II. Entomological
studies at Changa MangaNational Forest, Punjab Province, Trans. R.
Soc. Trop.Med. Hyg. (1982) 76:437448.
[122] Reisen W.K., Chiles R.E., Martinez V.M., FangY., Green
E.N., Experimental infection of Californiabirds with western equine
encephalomyelitis and St.Louis encephalitis viruses, J. Med.
Entomol. (2003)40:968982.
[123] Reisen W.K., Fang Y., Martinez V.M., Avianhost and
mosquito (Diptera: Culicidae) vector compe-tence determine the
efficiency of West Nile and St.Louis encephalitis virus
transmission, J. Med. Ento-mol. (2005) 42:367375.
[124] Reisen W.K., Fang Y., Martinez V.M., Effectsof temperature
on the transmission of West Nile virusby Culex tarsalis (Diptera:
Culicidae), J. Med. Ento-mol. (2006) 43:309317.
[125] Reisen W.K., Barker C.M., Fang Y., MartinezV.M., Does
variation in Culex (Diptera: Culicidae)vector competence enable
outbreaks of West Nile virusin California?, J. Med. Entomol. (2008)
45:11261138.
[126] Reisen W.K., Cayan D., Tyree M., BarkerC.M., Eldridge B.,
Dettinger M., Impact of climatevariation on mosquito abundance in
California, J.Vector Ecol. (2008) 33:8998.
[127] Reisen W.K., Lothrop H.D., Wheeler S.S.,Kennsington M.,
Gutierrez A., Fang Y., et al.,Persistent West Nile virus
transmission and theapparent displacement St. Louis encephalitis
virus insoutheastern California, 20032006, J. Med. Entomol.(2008)
45:494508.
[128] Reisen W.K., Carroll B.D., Takahashi R., FangY., Garcia
S., Martinez V.M., Quiring R., RepeatedWest Nile virus epidemic
transmission in KernCounty, California, 20042007, J. Med.
Entomol.(2009) 46:139157.
Factors impacting West Nile virus circulation Vet. Res. (2009)
40:43
(page number not for citation purpose) Page 17 of 19
-
[129] Rice C.M., Flaviviridae: the viruses and theirreplication,
in: Fields B.N., Knipe D.M., Howley P.M.(Eds.), Fields virology,
Lippincott-Raven, Philadel-phia, PA, 1996, pp. 931959.
[130] Roehrig J.T., Staudinger L.A., Hunt A.R.,Mathews J.H.,
Blair C.D., Antibody prophylaxis andtherapy for flavivirus
encephalitis infections, Ann.N.Y. Acad. Sci. (2001) 951:286297.
[131] Roehrig J.T., Layton M., Smith P., CampbellG.L., Nasci R.,
Lanciotti R.S., The emergence of WestNile virus in North America:
ecology, epidemiology,and surveillance, Curr. Top. Microbiol.
Immunol.(2002) 267:223240.
[132] Root J.J., Oesterle P.T., Nemeth N.M., KlenkK., Gould
D.H., McLean R.G., et al., Experimentalinfection of fox squirrels
(Sciurus niger) with WestNile virus, Am. J. Trop. Med. Hyg. (2006)
75:697701.
[133] Rossini G., Cavrini F., Pierro A., Macini P.,Finarelli A.,
Po C., et al., First human case of WestNile virus neuroinvasive
infection in Italy, September2008 case report, Euro Surveill.
(2008) 13:19002.
[134] Savage H.M., Ceianu C., Nicolescu G.,Karabatsos N.,
Lanciotti R., Vladimirescu A., et al.,Entomologic and avian
investigations of an epidemicof West Nile fever in Romania in 1996,
with serologicand molecular characterization of a virus isolate
frommosquitoes, Am. J. Trop. Med. Hyg. (1999) 61:600611.
[135] Scherret J.H., Poidinger M., Mackenzie J.S.,Broom A.K.,
Deubel V., Lipkin W.I., et al., Therelationships between West Nile
and Kunjin viruses,Emerg. Infect. Dis. (2001) 7:697705.
[136] Senne D.A., Pedersen J.C., Hutto D.L., TaylorW.D., Schmitt
B.J., Panigrahy B., Pathogenicity ofWest Nile virus in chickens,
Avian Dis. (2000)44:642649.
[137] Shaman J., Day J.F., Stieglitz M., The spatial-temporal
distribution of drought, wetting, and humancases of St. Louis
encephalitis in southcentral Florida,Am. J. Trop. Med. Hyg. (2004)
71:251261.
[138] Shaman J., Day J.F., Stieglitz M., Drought-induced
amplification and epidemic transmission ofWest Nile virus in
southern Florida, J. Med. Entomol.(2005) 42:134141.
[139] Shi P.Y., Brinton M.A., Veal J.M., Zhong Y.Y.,Wilson W.D.,
Evidence for the existence of a pseudo-knot structure at the 30
terminus of the flavivirusgenomic RNA, Biochemistry (1996)
35:42224230.
[140] Shirako Y., Strauss J.H., Requirement for anaromatic amino
acid or histidine at the N terminus of
Sindbis virus RNA polymerase, J. Virol. (1998)72:23102315.
[141] Singh I.R., Suomalainen M., Varadarajan S.,Garoff H.,
Helenius A., Multiple mechanisms for theinhibition of entry and
uncoating of superinfectingSemliki Forest virus, Virology (1997)
231:5971.
[142] Smithburn K.C., Hughs T.P., Burke A.W., PaulJ.H., A
neurotropic virus isolated from the blood of anative of Uganda, Am.
J. Trop. Med. Hyg. (1940)20:471492.
[143] Solomon T., Vaughn D.W., Pathogenesis andclinical features
of Japanese encephalitis and WestNile virus infections, Curr. Top.
Microbiol. Immunol.(2002) 267:171194.
[144] Spielman A., Andreadis T.G., Apperson C.S.,Cornel A.J.,
Day J.F., Edman J.D., et al., Outbreak ofWest Nile virus in North
America, Science (2004)306:14731475.
[145] Steele K.E., Linn M.J., Schoepp R.J., KomarN., Geisbert
T.W., Manduca R.M., et al., Pathology offatal West Nile virus
infections in native and exoticbirds during the 1999 outbreak in
New York City,New York, Vet. Pathol. (2000) 37:208224.
[146] Sundin D.R., Beaty B.J., Interference to
oralsuperinfection of Aedes triseriatus infected with LaCrosse
virus,Am. J. Trop.Med.Hyg. (1988) 38:428432.
[147] Swayne D.E., Beck J.R., Smith C.S., ShiehW.J., Zaki S.R.,
Fatal encephalitis and myocarditis inyoung domestic geese (Anser
anser domesticus)caused by West Nile virus, Emerg. Infect.
Dis.(2001) 7:751753.
[148] Taylor R.M., Hurlbut H.S., Dressler H.R.,Spangler E.W.,
Thrasher D., Isolation of West Nilevirus from Culex mosquitoes, J.
Egypt Med. Assoc.(1953) 36:199208.
[149] Taylor R.M., Work T.H., Hurlbut H.S., Rizk F.,A study of
the ecology of West Nile virus in Egypt,Am. J. Trop. Med. Hyg.
(1956) 5:579620.
[150] Tempelis C.H., Francy D.B., Hayes R.O., LofyM.F.,
Variations in feeding patterns of seven culicinemosquitoes on
vertebrate hosts in Weld and LarimerCounties, Colorado, Am. J.
Trop. Med. Hyg. (1967)16:111119.
[151] Tesh R.B., Arroyo J., Travassos Da Rosa A.P.,Guzman H.,
Xiao S.Y., Monath T.P., Efficacy of killedvirus vaccine, live
attenuated chimeric virus vaccine,and passive immunization for
prevention of West Nilevirus encephalitis in hamster model, Emerg.
Infect.Dis. (2002) 8:13921397.
[152] Tesh R.B., Travassos da Rosa A.P., Guzman H.,Araujo T.P.,
Xiao S.Y., Immunization with heterologous
Vet. Res. (2009) 40:43 A.C. Brault
Page 18 of 19 (page number not for citation purpose)
-
flaviviruses protective against fatal West Nile enceph-alitis,
Emerg. Infect. Dis. (2002) 8:245251.
[153] Tiawsirisup S., Platt K.B., Tucker B.J., RowleyW.A.,
Eastern cottontail rabbits (Sylvilagus floridanus)develop West Nile
virus viremias sufficient for infect-ing select mosquito species,
Vector Borne ZoonoticDis. (2005) 5:342350.
[154] Tsai T.F., Popovici F., Cernescu C., CampbellG.L., Nedelcu
N.I., West Nile encephalitis epidemic insoutheastern Romania,
Lancet (1998) 352:767771.
[155] Turell M.J., OGuinn M., Oliver J., Potentialfor New York
mosquitoes to transmit West Nile virus,Am. J. Trop. Med. Hyg.
(2000) 62:413414.
[156] Umrigar M.D., Pavri K.M., Comparative bio-logical studies
on Indian strains of West Nile virusisolated from different
sources, Indian J. Med. Res.(1977) 65:596602.
[157] Van Regenmortel M.H.V., Introduction to thespecies concept
in virus taxonomy, in: vanRegenmortel M.H.V., Fauquet C.M., Bishop
D.H.L.,Carstens E.B., Estes M.K., Lemon S.M., et al. (Eds.),Virus
taxonomy, classification and nomenclature ofviruses, , Seventh
Report of the International Com-mittee on Taxonomy of Viruses,
Academic Press, SanDiego, 2000, pp. 316.
[158] Verma S., Lo Y., Chapagain M., Lum S.,Kumar M., Gurjav U.,
et al., West Nile virus infectionmodulates human brain
microvascular endothelialcells tight junction proteins and cell
adhesion mole-cules: transmigration across the in vitro
blood-brainbarrier, Virology (2009) 385:425433.
[159] Weaver S.C., Brault A.C., Kang W., HollandJ.J., Genetic
and fitness changes accompanying
adaptation of an arbovirus to vertebrate and inverte-brate
cells, J. Virol. (1999) 73:43164326.
[160] Weiner L.P., Cole G.A., Nathanson N., Exper-imental
encephalitis following peripheral inoculationof West Nile virus in
mice of different ages, J. Hyg.(Lond.) (1970) 68:435446.
[161] Westaway E.G., Flavivirus replication strategy,Adv. Virus
Res. (1987) 33:4590.
[162] Westaway E.G., Mackenzie J.M., KhromykhA.A., Replication
and gene function in Kunjin virus,Curr. Top. Microbiol. Immunol.
(2002) 267:323351.
[163] Wilcox B.R., Yabsley M.J., Ellis A.E.,Stallknecht D.E.,
Gibbs S.E., West Nile virus antibodyprevalence in American crows
(Corvus brachyrhyn-chos) and fish crows (Corvus ossifragus) in
Georgia,USA, Avian Dis. (2007) 51:125128.
[164] Work T.H., Hurlbut H.S., Taylor R.M., Isola-tion of West
Nile virus from hooded crow and rockpigeon in the Nile delta, Proc.
Soc. Exp. Biol. Med.(1953) 84:719722.
[165] Work T.H., Hurlbut H.S., Taylor R.M., Indig-enous wild
birds of the Nile Delta as potential WestNile virus circulating
reservoirs, Am. J. Trop. Med.Hyg. (1955) 4:872888.
[166] Xiao S.Y., Guzman H., Zhang H., Travassos daRosa A.P.,
Tesh R.B., West Nile virus infection in thegolden hamster
(Mesocricetus auratus): a model forWest Nile encephalitis, Emerg.
Infect. Dis. (2001)7:714721.
[167] Xie H., Ryman K.D., Campbell G.A., BarrettA.D., Mutation
in NS5 protein attenuates mouseneurovirulence of yellow fever 17D
vaccine virus,J. Gen. Virol. (1998) 79:18951899.
Factors impacting West Nile virus circulation Vet. Res. (2009)
40:43
(page number not for citation purpose) Page 19 of 19