The Minus Sense and Ambisense RNA Viruses re are 7 families of minus strand RNA viruses All minus strand RNA viruses are enveloped with helical nucleocapsids. Families may differ in morphology of the virion, however. No polyproteins are made and the viruses do not encode proteases. Because the viral genomes are not mRNAs, all must contain enzymes within the virion to synthesize mRNA. Four families have a single piece of RNA as their genome and are grouped into the order Mononegavirales. The remaining three familes have segmented genomes. Minus strand or ambisense viruses infect vertebrates or plants. Some are arboviruses and thus infect arthropods as well. All RNA synthesis takes place within nucleocapsids. The genome is never released free into the cytoplasm.
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The Minus Sense and Ambisense RNA Viruses There are 7 families of minus strand RNA viruses All minus strand RNA viruses are enveloped with helical nucleocapsids.
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The Minus Sense and Ambisense RNA Viruses
There are 7 families of minus strand RNA viruses
All minus strand RNA viruses are enveloped with helical nucleocapsids. Families may differ in morphology of the virion, however.
No polyproteins are made and the viruses do not encode proteases.
Because the viral genomes are not mRNAs, all must contain enzymes within the virion to synthesize mRNA.
Four families have a single piece of RNA as their genome and are grouped into the order Mononegavirales. The remaining three familes have segmented genomes.
Minus strand or ambisense viruses infect vertebrates or plants. Some are arboviruses and thus infect arthropods as well.
All RNA synthesis takes place within nucleocapsids. The genome is never released free into the cytoplasm.
Vertebrates Some arthropod-borneVesiculovirus VSIVLyssavirus Contact with salivaVertebrates RabiesEphemerovirus Arthropod-borneCattleBEFVNovirhabdovirus FishIHNV
Diagram of the VSV Genome and the Structure of the Gene Junctions
Replication of Rhabdovirus RNA
Switch from mRNA synthesis to RNA replication occurs when sufficient N protein has been made to encapsidate the newly synthesized RNA.
The (+)RNA is then encapsidated during synthesis and a perfect complementary copy of the genome is produced. Stop signals, poly(A) signals, reinitiation signals are all ignored.
The encapsidated antigenomic RNA can be used in turn to synthesize more genomic RNA
Synthesis of genomic (-)RNA also requires encapsidation of the newly synthesized RNA during synthesis.
Thus, protein synthesis is required for replication of the genome but not for synthesis of mRNAs.
Genomic RNA and antigenomic templates are never free but are always present in nucleocapsids, whereas mRNAs are not encapsidated.
Budding VSV
Rabies VirusThe most dangereous rhabdovirus is rabies virus and its ally bat lyssavirus
The virus is associated with wildlife--it is a zoonotic virusThe virus is usually transmitted to humans by the bite of a rabid animal--
there is no human-to-human transmission
The virus first replicates around the site of the bite
The probability of CNS infection depends upon the location of the bite
Once the symptoms of rabies occur the infection is uniformly fatal
Louis Pasteur developed an early vaccine against rabies
50,000 humans die each year of rabies
A modern vaccine is widely used to prevent rabies
One million people are inoculated each year following exposure
Because transfer to the brain in delayed, the vaccine can be administered postexposure
Transmission to the CNS may occur upon infection of axons near the site
Bats are an important reservoir. Transmission to humans from bats may sometimes occur through aerosols.
2000199019801970196019501940
10
20
30
40
50
60
Year
10,000
8000
6000
4000
2000DEATHSCASES
Human Rabies
Dogs
Wildlife
Nu
mb
er o
f H
um
an D
eath
s (c
ases
) p
er Y
ear
Nu
mb
er o
f A
nim
al C
ases
per
Yea
r
Rabies in the United States, 1940-1995
Ohio
North Carolina
Virginia
Pennsylvania
New York
Maine
New Hampshire
Massachusetts
Rhode Island
New Jersey
Connecticut
DelawareMaryland
Vermont
1977-1979
1980-1984
1985-1989
1990-1994
1994-1998
No raccoon rabies detected
West Virginia
Spread of Raccoon Rabies throughout the Atlantic Seaboard
Control of Rabies by Vaccination of Wildlife
Wildlife in areas of the U.S. and Europe have been vaccinated using baits containing vaccine.
The bait contains attenuated rabies virus or contains vaccinia virus that expresses rabies G protein.
The bait is often broadcast from planes.
Such programs have been moderately successful in containing the spread of rabies, but are expensive and manpower-intensive.
ParamyxovirusesParamyxoviruses have genomes of 15-20 kb and have 8-11 (or more) genes
Six genera are currently recognized
The family contains many important human pathogens
Many viruses cause respiratory disease including pneumonia
Mumps virus and measles virus are paramyxoviruses
Transmission of the viruses is by aerosols
To date, only mammals and birds are known to be infected by paramyxoviruses
Two recently identified viruses cause encephalitis in humans
Many are specific for a particular host
Many of the human viruses infect only humans
Virions are usually spherical when grown in culture, but clinical specimens are often filamentous
Genome Organizations of Five Genera of theParamyxoviridae.
RESPIROVIRUSHPIV-315462 nt2258572539353603515
LHNFMP/CNaa
RUBULAVIRUSSV-5
15246 nt510 392 529377
SH
44 565 2255N V/P M F HN L
aa
MORBILLIVIRUSMeV
15894 ntL
2183 N 525
P507
M335 553
F H617aa
MEGAMYXOVIRUS (Hendra virus, 18234nt)
N532
P/V/C707 546
FM352
G604
L2244 aa
PNEUMOVIRUS HRSV
15225ntNS1NS2
139124
N391
P241
M256 65
G299 574
F M2195/90
L2166
SH
aa
3’ 5’
MEASLESMORBILLIVIRUS
HPIV-2, HPIV-4, SV-5, (NDV)
SENDAI
HPIV- 3
MUMPS
HPIV- 1 C protein
P protein
C proteinP protein
V protein+ 1 G
RESPIROVIRUS
RUBULAVIRUS
ORF1 ORF2 ORF3 Cysteine-rich domain
C proteinP protein
V protein+ 1 G
* **** *
V protein
+ 4G I protein
+ 2G P protein
* **** *
V protein+ 2G
P protein
* **** *
C proteinP protein
D protein+ 2G
V protein+ 1 G
* **** *
* **** *
MEGAMYXOVIRUSNIPAH
* **** *
P proteinC protein
V protein+ 1 G
****
Translation Strategy of the P Gene of Paramyxoviruses
Pneumovirinae
Paramyxovirinae
Subfamily
Pneumovirus Metapneumovirus
Genus Species 100 nt substitutions
NDV HPIV-2
SV-5 MuV
HPIV-4a HPIV-4b
HPIV-1 SeV
HPIV-3 CDV PDV
RPV MeV
PPRV DMV
TRTV HRSV
Respirovirus
Morbillivirus
Megamyxovirus Hendra Nipah
Rubulavirus
Phylogenetic Tree of the Paramyxoviridae (Derived from the sequences of the N ORF)
Measles virus
Measles virus was once epidemic throughout the world. Very few people escaped infection by it.
It is spread by aerosols and begins infection in the URT. It then becomes systemic and infects many organs.
It causes a serious illness. It leads to temporary suppression of the immune system and infected persons may succumb to secondary infectionn.Infection of the CNS can lead to neurological sequella, including SSPE.
A live vaccine, part of the MMR vaccine, has almost eradicated measles from the Americas. The virus is still epidemic in Africa and parts of Asia, however, and imported cases have resulted in small epidemics in the U.S.
Worldwide 2.5 million/year died from measles.
Measles Virus History
Measles virus is a human virus and humans are the only reservoir in nature.
Infection results in solid, life-long immunity.
Spread is by direct person-to-person contact.
Therefore a minimum population size of about 500,000 is required to maintain the virus, and measles could not have existed before human populations reached this size.
This may have occurred about 5000 years ago following domestication of plants and animals.
When the virus was first introduced into naïve populations during European exploration 200-500 years ago, the death toll was enormous. One result, aided by smallpox, was the depopulation of the Americas.
20
15
10
5
01 2 3 4 5 6 70
Iceland
New HebridesNew CaledoniaSolomon Islands
French Polynesia
Tonga
Western Samoa
Mean Distance Between New Susceptibles (Kilometers)
Du
rati
on
of
Ep
idem
ics
of
Measl
es
(Mon
ths)
B.
100
80
60
40
20
04 8 12 16
Guam
Bermuda
A.
New Susceptibles in Thousands per Year
Perc
en
t of
Mon
ths
wit
h C
ase
s of
Measl
es
Effect of Population Size and Density on the Epidemiology of Measles
Measles vaccine licensed
1982 1987 1992 1997Rep
orte
d C
ases
(th
ousa
nd
s)
Rep
orte
d C
ases
(th
ousa
nd
s)
30
20
10
0
1962 1967 1972 1977 1982 1987 1992 1997
500
450
400
350
300
250
200
150
100
50
0
Cases of Measles in the United States, 1962 to 1997
5 10 15 20 25 30 35 40Age (Months)
EZ-HT
SW-HT
Standard
Mort
ali
ty (
per
10
00
ch
ild
ren
at
5 m
on
ths)
200
150
100
50
0
Trial in Senegal with High-Titer Measles Vaccine
Rep
ort
ed
case
s /1
00
,00
0 p
op
ula
tion
Mumps vaccine licensed in 1967
1968 1972 1976 1980 1984 1988 1992 1996
1982 1987 1992 1997
76
54
32
10
Rep
ort
ed
case
s /1
00
,00
0 p
op
ula
tion 90
80
70
60
50
40
30
20
10
0
Incidence of Mumps in the United States, 1968-1998
Respiratory Syncytial Virus
RSV is the leading cause of pneumonia in infants worldwide.
Infection begins in the URT but spreads to the LRT in ~1/3 of primary infections.
Immunity following infection is incomplete and children and adults suffer recurrent infections.
Disease symptoms are usually milder in second and subsequent infections, however.
RSV infection of immunocompromised persons is very serious.
No vaccine exists. Clinical trials with an inactivated virus vaccine gave the disastrous result that vaccinated individuals suffered more serious illness upon subsequent infection by RSV.