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NORTON UNIVERSITY

VIROLOGY COURSE

2014-2015

General virology, History, Taxonomy

Ph. VONG Dany

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• Virus : a noncellular genetic element that infects a cell for its

own replication, it has an extracellular state.

• A virus particle containing nucleic acid surrounded by protein

and other macromolecular components is called virion.

• Viruses have a heavy dependence on host-cell structural and

metabolic components.

• Viruses can confer important new properties on their host cell.

• Viruses may be non productive, latent, oncogenic, chronic or

lytic.

Definition

Nucleic Acid

Spike

Projections

Protein

Capsid

Lipid Envelope

Virion

Associated

Polymerase

Virion structure

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I. GENERAL VIROLOGY

1840’s:

Agents not visible under microscope

Concept of virology. History

1930-1955:

1. Viruses contain proteins that can be:

• precipitated,

• concentrated,

• Inactivated (resistance to physical and chemical agents),

• neutralized (production of antibodies in animals),

• electrophoresed

2. Viruses contain phosphorus

3. Viruses contain ribonucleic acids or deoxyribonucleic acids

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4. Electron microscopy (1937)

5. Viruses have different structures

6.The use of animals for virus cultivation (1931)

Mouse (leukemia lymphoid virus)

Embryonated eggs (pox virus)

7. The use of cell culture for virus cultivation (1948)

Poliovirus

Vaccine development in

animals (rabies, YFV)

embryonated chicken eggs (YFV, smallpox, influenza)

cell culture (poliovirus)

6Deoxyribonucleic acid Ribonucleic acid

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DNA Viruses: RNA Viruses:

Adenoviruses Coronaviruses

Iridoviruses Filoviruses

Herpesviruses Orthomyxoviruses

Papovaviruses Paramyxoviruses

Parvoviruses Picornaviruses

Poxviruses Retroviruses

Viral Hepatitis Rhabdoviruses

"Arboviruses" Arenaviruses, Bunyaviruses, Flaviviruses, Togaviruses

Diarrhoea Viruses Astroviruses, Caliciviruses, Reoviruses (inc. Rotaviruses)

•Taxonomic order (Order, Family, Subfamily, Genus, Species, strain, variant)

•General host range (bacteria, plant, animal; host range, pathogenesis,

transmission, habitat…)

•Disease order

II. VIRUS TAXONOMY

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Virus classification

International Committee on Taxonomy of Viruses

I: dsDNA viruses (e.g. Adenoviruses, Herpesviruses, Poxviruses)

II: ssDNA viruses (+)sense DNA (e.g. Parvoviruses)

III: dsRNA viruses (e.g. Reoviruses)

IV: (+)ssRNA viruses (+)sense RNA (e.g. Picornaviruses, Togaviruses)

V: (−)ssRNA viruses (−)sense RNA (e.g. Orthomyxoviruses, Rhabdoviruses)

VI: ssRNA-RT viruses (+)sense RNA with DNA intermediate in life-cycle (e.g.

Retroviruses)

VII: dsDNA-RT viruses (e.g. Hepadnaviruses)

Baltimore classification (1970’s)

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Most families have distinct virion morphology, genome structure, and replication strategy

VIII. Subviral agents

(Viroids, satellites

Prions)

IX Unassigned virus

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DNA viruses

adenovirus

Papillomavirus

Herpesvirus

Parvo virus

Hepatitis B virus

Molluscum contagiosum

(Pox virus)

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RNA viruses

Influenza viruses

Rotavirus

Enterovirus

Paramyxovirus

Rift valley fever

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Basic virus structures

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Enveloped helical virus Enveloped icosahedral virus

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Icosahedric symmetry of viruses by cryo-electron microscopy

T=3 symmetry

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Classification by Host range:

Algae

Archeal

Bacteria

Fungi

Invertebrate

Plant

Animal

Protozoa

Vertebrates

Some viruses can replicate in different types of hosts:

ex: Flaviviruses, Bunyaviridae, and Togaviridae

Virus classification

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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 gastrointestinal tract

• – Do not need to kill cells in order to spread

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• Capsid is resistant to• Drying

• Heat

• Detergents

• Acid

• 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

Properties of nacked capsid viruses

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Cancer:

Epstein Barr: Burkitt lymphoma (1962-68) and mononucleosis

Human T-cell leukemia (1977-1980)

Hepatocellular carcinoma-Hepatitis B (1967)

Papillomavirus

Hepatitis C (1985): a different story from RNA virus

Acute diseases:

Ex: Influenza, dengue

Chronic disease:

Ex: Herpes, HIV

Symptomatic diseases:

Acute respiratory infection

Viral encephalitis

Hepatitis

Diarrhea…

III. VIRUSES AND DISEASES

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• Respiratory transmission

Influenza A virus

• Faecal-oral transmission

Enterovirus

• Blood-borne transmission

Hepatitis B virus

• Sexual Transmission

HIV

• Animal or insect vectors

Rabies virus

Transmission of viruses

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Major determinants in viral tropism

Receptor and co-receptor

Cell surface receptors binding directly to native virus

Co-receptors bind as a result of primary binding to native or altered

form of virus protein

Entry

Injection of genetic material

Membrane disruption

Pores

Fusion

Endocytosis

Uncoating

RNA replication

Assembly-Maturation

▪ Attachment, sometimes called absorption: The virus attaches to receptors on the

host cell wall.

• Injection: The nucleic acid of the virus moves through the plasma membrane and

into the cytoplasm of the host cell.

• Transcription: Within minutes of phage entry into a host cell, a portion is

transcribed into mRNA, which is then translated into proteins specific for the

infecting phage.

• Replication: The viral genome contains all the information necessary to produce

new viruses. Once inside the host cell, the virus induces the host cell to

synthesize the necessary components for its replication.

• Assembly: The newly synthesized viral components are assembled into new

viruses.

• Release: Assembled viruses are released from the cell and can now infect other

cells, and the process begins again.

Life Cycle

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VIRAL

LIFE

CYCLE

ATTACHMENT

PENETRATION HOST

FUNCTIONS

ASSEMBLY

(MATURATION)

Transcription

REPLICATION

RELEASE

UNCOATING

Translation

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•G-protein-coupled receptors (chemokine receptors for retroviruses)

•Proteins with multiple membrane-spanning domains (Transporter for retroviruses)

•Immunoglobin-related proteins (UK function or ICAM and CD4 for Picorna-, Adeno-,

Corona-, Retro-, Herpes-, Flavi-viruses)

•Low-density lipoprotein receptor-related proteins (Retro- and Picorna- viruses)

•Integrins (Vitroectin and laminin binding for Adeno-, Picorna-viruses)

•TNF-receptors (Retro-, Herpes viruses)

•Glycoaminiglycans (low-binding receptor for flaviviridae like dengue or Hepatitis C

•CD81, Claudin-1 and occluding are tight-junction for hepatitis C

•Small consensus repeat-containing proteins (Complement inhibition for Picorna-,

Herpes-, Paramyxo-viruses)

•Sialic acid-containing oligosaccharides (Orthomyxo-, Paramyxo-, Reo-, Papova-,

Parvo-, Corona-viruses)

•Galactosyl ceramide (Retroviruses)

•Heparane sulfate (Herpes-, flaviviruses)

•Miscellaneous (Metalloprotease: Coronavirus, a-dystroglycan: Arenaviruses,

Laminin binding: Togavirus; Ephrin2, TKR: Nipah virus)

Virus receptors

HCV requires multiple host cellular factors for entry

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There are two types of viral membrane proteins (I and II)

VIRUS ENVELOPE

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Virus entry

• Endocytosis at the plasma membrane

• Fusion at the cell membrane.

• Endocytosis and fusion at the membrane of the endosome (acidification)

> Transportation into the cytoplasm, decapsidation

> Transportation to the nucleus

Fusion requires conformational changes of the virus coat protein(s)

> One or two or several proteins (receptors)

> acidic or neutral pH

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• Virus particles consist mainly of nucleic acid and protein

• Some viruses have particles that are surrounded by a membrane.

• Virus proteins protect the viral genome, identify the appropriate target cells, and get the genome into the target cells.

• Some viruses contain proteins with enzymatic functions that are needed for genome replication and enter host cells.

• Membrane-bound viruses are formed by budding from a cell membrane.

Key points

• Viruses infect all known species

• Viruses can be classified by a number of different methods

including disease, host range, morphology, and nature of

the genome in association with the method of replication

and transcription

• Virus genomes consist of either DNA or RNA and may be

single stranded or double stranded

• Some viruses convert their genomes from RNA to DNA, or

vice versa, for replication and transcription

Key points (cont.)