Page 1
Principles of Virology
Part I
Prof. Richard C. Condit
The screen versions of these slides have full details of copyright and acknowledgements 1
1
Principles of Virology
Part I
Prof. Richard C. ConditDepartment of Molecular Genetics & Microbiology
University of Florida, Gainesv ille, FL
2
Principles of virology I
• Viruses defined
• History
• Virus structure
• Virus classification
• Virus replication
• Pathogenesis
• Emerging infections
3
Viruses defined
Obligate intracellular parasites
Page 2
Principles of Virology
Part I
Prof. Richard C. Condit
The screen versions of these slides have full details of copyright and acknowledgements 2
4
Principles of virology I
• Viruses defined
• History
• Virus structure
• Virus classification
• Virus replication
• Pathogenesis
• Emerging infections
5
Delbruck,
Luria
Woodruff,
Goodpasture
Loeffler, Frosch
Beijerinck
Baltimore,TeminDulbeccoEndersEllis , DelbruckTwort, d’HerelleReed, CarrollIvanovsky
Montagnier,GalloWHOKnoll, RuskaJenner
1890 1900 1910 1920 1930 1940 1950 1960 1970 1980 1990
1983: HIV
Montagnier Gallo
1979: Smallpox eradication
World Health Organization
1970: Retroviral reverse transcriptase
TeminBaltimore
1952: Animal virus plaque assay
Dulbecco
1948: Poliovirus culture
Enders
1943-1970: Phage group
Delbruck, Luria
1933: Electron micrscope
Knoll, Ruska
1939: One step growth
DelbruckEllis
1931: Egg culture
Goodpastur eAlice Woodruff Edward Jenner
1796: Smallpox vaccinati on
1892: Ivanovsky
TMV filterable1901: Yellow fever virus
Reed Carroll
1915, 1917: Bacteriophage
Twort d’Herelle
1898: FMDV, TMV are parasites
FroschLoeffler Beijerinck
History
6
Principles of virology I
• Viruses defined
• History
• Virus structure
• Virus classification
• Virus replication
• Pathogenesis
• Emerging infections
Page 3
Principles of Virology
Part I
Prof. Richard C. Condit
The screen versions of these slides have full details of copyright and acknowledgements 3
7
Basic virus structure
Capsid
proteinNucleocapsid
Naked
capsid virus
DNA
RNA
or =+
NucleocapsidLipid membrane,
glycoproteinsEnveloped virus+
8
Capsid symmetry
Icosahedral Helical
Naked capsid
Enveloped
Lipid
Glycoprotein
Matrix
9
Icosahedral naked capsid viruses
Adenovirus
electron micrograph
Foot and mouth disease virus
crystallograph ic model
Page 4
Principles of Virology
Part I
Prof. Richard C. Condit
The screen versions of these slides have full details of copyright and acknowledgements 4
10
Helical naked capsid viruses
Tobacco mosaic virus
electron micrograph
Tobacco mosaic virus
model
RNA Protein
11
Icosahedral enveloped viruses
Herpes simplex virus
electron micrograph
Herpes simplex virus
nucleocapsid cryoEM model
12
Helical enveloped viruses
Influenza A virus
electron micrograph
Paramyxovirus
electron micrograph
Page 5
Principles of Virology
Part I
Prof. Richard C. Condit
The screen versions of these slides have full details of copyright and acknowledgements 5
13
Properties of enveloped viruses
• Envelope is sensitive to
– Drying
– Heat
– Detergents
– Acid
• Consequences
– Must stay wet during transmission
– Transmission in large droplets and secretions
– Cannot survive in the gastrointest inal tract
– Do not need to kill cells in order to spread
– May require both a humoral and a cellular immune response
14
Properties of naked capsid viruses
• Capsid is resistant to
– Drying
– Heat
– Detergents
– Acids
– Proteases
• Consequences
– Can survive in the gastrointestinal tract
– Retain infectivity on drying
– Survive well on environmental surfaces
– Spread easily via fomites
– Must kill host cells for release of mature virus particles
– Humoral antibody response may be sufficient
to neutralize infection
15
Principles of virology I
• Viruses defined
• History
• Virus structure
• Virus classification
• Virus replication
• Pathogenesis
• Emerging infections
Page 6
Principles of Virology
Part I
Prof. Richard C. Condit
The screen versions of these slides have full details of copyright and acknowledgements 6
16
Uniqueness of viruses defies application of traditional tools of taxonomy
EukaryaArchaea Bacteria
Protista Fungi Plantae Animalia
Viruses?
Virus classification: introduction
17
• Order
– Family
• Genus
–Species
Taxonomy is hierarchical
• Order
• Family
• Genus
• Species
18
Taxonomy is polythetic
• Virion morphology
– Size
– Shape
– Capsid symmetry
– Envelope
• Virion physical properties
– Genome structure
– Sensitivity to physical or chemical insults
– Specific features of viral lipids, carbohydrates, proteins
• Antigenic properties
• Biologic properties
– Replication strategy
– Host range
– Mode of transmission
– Pathogenicity
Polythetic:
Sharing a number of common characteristics, without any one characteristic being essential
for membership in the group or class
Page 7
Principles of Virology
Part I
Prof. Richard C. Condit
The screen versions of these slides have full details of copyright and acknowledgements 7
19
Nomenclature
• Order = ...virales
• Family = ...viridae
• Subfamily = ...virinae
• Genus = ...virus
Example:
order Mononegavirales, family Paramyxoviridae,
subfamily Pneumovirinae, genus Pneumovirus,
species Human respiratory syncytial virus
20
Order Family Subfamily Genus
Taxonomy of the order Mononegavirales
a V, vertebrate; I, insect; P, plant
HostaMononegavirales
Bornaviridae
Bornavirus Borna disease virus V
Rhabdoviridae
Vesiculovirus Vesicular stomatitis Indiana virus V, I
Lyssavirus Rabies v irus V
Ephemerovirus Bovine ephemeral fever v irus V, I
Novirhabdovirus Infectious hematopoietic necrosis v irus V
Cytorhabdovirus Lettuce necrotic yellows virus P, I
Nucleorhabdovirus Potato yellow dwarf v irus P, I
Filoviridae
Marburghvirus Lake Victoria marburgvirus V
Ebolavirus Zaire ebolavirus V
Paramyxoviridae
Paramyxovirinae
Rubulavirus Mumps virus V
Avulavirus Newcastle disease virus V
Sendai v irus V
Henipavirus Hendra virus V
Morbilliv irus Measles v irus V
Pneumovirinae
Pneumovirus Human respiratory syncytial v irus V
Metapneumovirus Avian metapneumovirus V
Type species
21
Classification of human viruses"Group" Family Genome Genome size (kb) Capsid Envelope
dsDNA
Poxvir idae dsDNA, linear 130 t o 375 Ovoid Yes
Herpesvir idae dsDNA, linear 125 t o 240 I cosahedral Yes
Adenoviri dae dsDNA, linear 26 to 45 I cosahedral No
Polyomav iridae dsDNA, circular 5 I cosahedral No
Papil lomavir idae dsDNA, circular 7 to 8 I cosahedral No
ssDNA
Anell ovirus ssDNA c irc ular 3 to 4 I sometr ic No
Parvov iradae ssDNA, linear, (- or +/-) 5 I cosahedral No
Retro
Hepadnavir idae dsDNA (partial), circular 3 to 4 I cosahedral Yes
Retroviridae ssRNA (+), diploid 7 to 13 Spherical, rod or cone shaped Yes
dsRNA
Reovir idae dsRNA, segment ed 19 to 32 I cosahedral No
ssRNA (-)
Rhabdov iridae ssRNA (-) 11 to 15 Helic al Yes
Filovir idae ssRNA (-) 19 Helic al Yes
Paramyxovir idae ssRNA (-) 10 to 15 Helic al Yes
Ort homyxovir idae ssRNA (-) , s egmented 10 to 13.6 Helic al Yes
Bunyav iridae ssRNA (-, ambi) , s egmented 11 to 19 Helic al Yes
Arenaviridae ssRNA (-, ambi) , s egmented 11 C ircular, nucleosomal Yes
Deltavirus ssRNA (-) c ircular 2 Spherical Yes
ssRNA (+)
Picornavir idae ssRNA (+) 7 to 9 I cosahedral No
Calci viridae ssRNA (+) 7 to 8 I cosahedral No
Hepev irus ssRNA (+) 7 I cosahedral No
As trovir idae ssRNA (+) 6 to 7 I sometr ic No
Coronav iridae ssRNA (+) 28 to 31 Helic al Yes
Flavivir idae ssRNA (+) 10 to 12 Spherical Yes
Togavir idae ssRNA (+) 11 to 12 I cosahedral Yes
Page 8
Principles of Virology
Part I
Prof. Richard C. Condit
The screen versions of these slides have full details of copyright and acknowledgements 8
22
Major diseases caused by human viruses
23
Vertebrate
viruses
24
Complete taxonomy
• 5450 v iruses
– 3 orders
– 73 families
– 9 subfamilies
– 287 genera
– 1950 species
Page 9
Principles of Virology
Part I
Prof. Richard C. Condit
The screen versions of these slides have full details of copyright and acknowledgements 9
25
Principles of virology I
• Viruses defined
• History
• Virus structure
• Virus classification
• Virus replication
• Pathogenesis
• Emerging infections
26
Virus replication: general
27
• dsDNA
• ssDNA
• (+)ssRNA
• (-)ssRNA
• dsRNA
• RNA retro
• DNA retro
Virus replication:
variations on the theme
Page 10
Principles of Virology
Part I
Prof. Richard C. Condit
The screen versions of these slides have full details of copyright and acknowledgements 10
28
dsDNA virus replication
dsDNA dsDNA
(+)mRNA
29
ssDNA virus replication
(+)mRNA
dsDNAssDNA
(+)
30
(+)ssRNA virus replication
(+)RNA (-)RNA (+)RNA
Page 11
Principles of Virology
Part I
Prof. Richard C. Condit
The screen versions of these slides have full details of copyright and acknowledgements 11
31
(-)ssRNA virus replication
(+)mRNA
(-)RNA
(+)RNA (-)RNA
32
dsRNA virus replication
(+)mRNAdsRNA
dsRNA
33
(+)ssRNA retrovirus replication
(+)RNA
dsDNA
ssDNA
(+)mRNA
(+)RNA
Page 12
Principles of Virology
Part I
Prof. Richard C. Condit
The screen versions of these slides have full details of copyright and acknowledgements 12
34
dsDNA retrovirus replication
dsDNA
ssDNA
(+)mRNA
(+)RNA
dsDNA
35
Time
Virus concentration
Virus growth
Eclipse
Plateau
1,000 – 100,000 viruses/cell5 – 24 hours
36
Principles of virology I
• Viruses defined
• History
• Virus structure
• Virus classification
• Virus replication
• Pathogenesis
• Emerging infections
Page 13
Principles of Virology
Part I
Prof. Richard C. Condit
The screen versions of these slides have full details of copyright and acknowledgements 13
37
Viral pathogenesis
• Cycle of infection
– Entry
– Primary site replication
– Spread within the host
– Shedding
– Transmission
• Patterns of disease
• Effects on cells
38
Entry
• Mucous membranes or skin
– Respiratory
– Oral
– Sexual
– Ocular
– Percutaneous
• Needles, wounds, bites
39
Replication and spread
Secondary sites
Spread
Entry Shedding
Shedding
Local
Lymphatic
Neuronal
Blood (viremia)
Primary site
Page 14
Principles of Virology
Part I
Prof. Richard C. Condit
The screen versions of these slides have full details of copyright and acknowledgements 14
40
Shedding, transmission
• Routes
– Respiratory
– Gastrointestinal (oral-fecal)
– Urogenital
– Skin
• Mechanisms
– Indirect contact
• Aerosols
• Fomites
– Direct contact
• Lesions
• Saliva
• Sex
• Animal or insect bites
• Maternal-neonatal
41
Mouspox
pathogenesis
42
Disease patterns
Acute infection
Disease
Time
Virus load
= Virus load = Disease episode
Disease Disease
Latent infection
Disease Disease?
Chronic infection
Disease?
Latency
Page 15
Principles of Virology
Part I
Prof. Richard C. Condit
The screen versions of these slides have full details of copyright and acknowledgements 15
43
Effects on cells
• Abortive infection
• Lytic infection
• Persistence
• Transformation
44
Principles of virology I
• Viruses defined
• History
• Virus structure
• Virus classification
• Virus replication
• Pathogenesis
• Emerging infections
45
Emergence defined
• Emergence of new viral diseases
– Evolution of new organisms
– Spread of known viruses to new geographic areas
– Ecological change resulting in exposure
to insects or animals harboring the virus
• Re-emergence of known viral diseases
– Development of resistance to vaccines or antiviral drugs
– Breakdown of public health measures
for previously controlled infections
Page 16
Principles of Virology
Part I
Prof. Richard C. Condit
The screen versions of these slides have full details of copyright and acknowledgements 16
46
Virus-host equilibrium
• Equilibrium human virus
– Virus has stable relationsh ip with human host
– Virus can maintain infection chain in humans
– Virus has no contemporary animal host
• Non-equilibrium human virus
– Virus has a stable relationship with animal host
– Virus can be strikingly lethal since it hasn't evolved
to coexist with humans
– Human to human transmission may be limited
– Virus will be in genetic flux until it reaches equilibrium
or human infection chain is broken
47
Factors influencing emergence
• Microbial adaptation and change
• Human susceptibility to infection
• Climate and weather
• Changing ecosystems
• Human demographics and behavior
• Economic development and land use
• International travel and commerce
• Technology and industry
• Breakdown of public health measures
• Poverty and social inequality
• War and famine
• Lack of political will
• Intent to harm
Microbial threats to health: emergence, detection, and response
Institute of Medicine, (2003)
48
Emerging viruses 1973-2006
• 1973 Rotavirus
• 1975 Parvovirus B19
• 1977 Ebola virus
• 1977 Hantaan virus
• 1980 HTLV-I
• 1982 HTLV-II
• 1983 HIV
• 1986 Herpesvirus-6
• 1988 Hepatitis E virus
• 1989 Sabiá virus
• 1990 Hepatitis C virus
• 1990 Guanarito virus
• 1993 Sin nombre virus
• 1994 Hendra virus
• 1995 Herpesvirus-8
• 1998 Nipah virus
• 1999 West Nile virus (N.A.)
• 2001 Metapneumovirus
• 2003 SARS-CoV
• 2004 Monkeypox (N.A.)
• 2005 Avian Influenza
• 2006 Epi Dengue-DHF
On average, one new virus every 19 months
Page 17
Principles of Virology
Part I
Prof. Richard C. Condit
The screen versions of these slides have full details of copyright and acknowledgements 17
49