Principles of Virology Part I Prof. Richard C. Condit · Principles of Virology Part I Prof. Richard C. Condit The screen versions of these slides have full details of copyright and

Principles of Virology

Part I

Prof. Richard C. Condit

The screen versions of these slides have full details of copyright and acknowledgements 1

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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


Part I



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• Viruses defined

• History

• Virus structure



• Pathogenesis


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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

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• Viruses defined

• History

• Virus structure



• Pathogenesis



Part I



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Basic virus structure

Capsid

proteinNucleocapsid

Naked

capsid virus

DNA

RNA

or =+

NucleocapsidLipid membrane,

glycoproteinsEnveloped virus+

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Capsid symmetry

Icosahedral Helical

Naked capsid

Enveloped

Lipid

Glycoprotein

Matrix

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Icosahedral naked capsid viruses

Adenovirus

electron micrograph

Foot and mouth disease virus

crystallograph ic model


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Helical naked capsid viruses

Tobacco mosaic virus

electron micrograph

Tobacco mosaic virus

model

RNA Protein

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Icosahedral enveloped viruses

Herpes simplex virus

electron micrograph

Herpes simplex virus

nucleocapsid cryoEM model

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Helical enveloped viruses

Influenza A virus

electron micrograph

Paramyxovirus

electron micrograph


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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

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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

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• Viruses defined

• History

• Virus structure



• Pathogenesis



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Uniqueness of viruses defies application of traditional tools of taxonomy

EukaryaArchaea Bacteria

Protista Fungi Plantae Animalia

Viruses?

Virus classification: introduction

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• Order

– Family

• Genus

–Species

Taxonomy is hierarchical

• Order

• Family

• Genus

• Species

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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


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Nomenclature

• Order = ...virales

• Family = ...viridae

• Subfamily = ...virinae

• Genus = ...virus

Example:

order Mononegavirales, family Paramyxoviridae,

subfamily Pneumovirinae, genus Pneumovirus,

species Human respiratory syncytial virus

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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

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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


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Major diseases caused by human viruses

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Vertebrate

viruses

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Complete taxonomy

• 5450 v iruses

– 3 orders

– 73 families

– 9 subfamilies

– 287 genera

– 1950 species


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• Viruses defined

• History

• Virus structure



• Pathogenesis


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Virus replication: general

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• dsDNA

• ssDNA

• (+)ssRNA

• (-)ssRNA

• dsRNA

• RNA retro

• DNA retro

Virus replication:

variations on the theme


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dsDNA virus replication

dsDNA dsDNA

(+)mRNA

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ssDNA virus replication

(+)mRNA

dsDNAssDNA

(+)

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(+)ssRNA virus replication

(+)RNA (-)RNA (+)RNA


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(-)ssRNA virus replication

(+)mRNA

(-)RNA

(+)RNA (-)RNA

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dsRNA virus replication

(+)mRNAdsRNA

dsRNA

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(+)ssRNA retrovirus replication

(+)RNA

dsDNA

ssDNA

(+)mRNA

(+)RNA


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dsDNA retrovirus replication

dsDNA

ssDNA

(+)mRNA

(+)RNA

dsDNA

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Time

Virus concentration

Virus growth

Eclipse

Plateau

1,000 – 100,000 viruses/cell5 – 24 hours

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• Viruses defined

• History

• Virus structure



• Pathogenesis



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Viral pathogenesis

• Cycle of infection

– Entry

– Primary site replication

– Spread within the host

– Shedding

– Transmission

• Patterns of disease

• Effects on cells

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Entry

• Mucous membranes or skin

– Respiratory

– Oral

– Sexual

– Ocular

– Percutaneous

• Needles, wounds, bites

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Replication and spread

Secondary sites

Spread

Entry Shedding

Shedding

Local

Lymphatic

Neuronal

Blood (viremia)

Primary site


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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

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Mouspox

pathogenesis

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Disease patterns

Acute infection

Disease

Time

Virus load

= Virus load = Disease episode

Disease Disease

Latent infection

Disease Disease?

Chronic infection

Disease?

Latency


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Effects on cells

• Abortive infection

• Lytic infection

• Persistence

• Transformation

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• Viruses defined

• History

• Virus structure



• Pathogenesis


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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


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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

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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)

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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


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Principles of Virology Part I Prof. Richard C. Condit · Principles of Virology Part I Prof. Richard C. Condit The screen versions of these slides have full details of copyright and