Introduction to viruses

BIO 370

Ramos

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General Structure of Viruses

• Size range –

– most <0.2 μm; requires electron microscope

• Virion – fully formed virus able to establish

an infection

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General Structure of Viruses

• Capsids

– All viruses have capsids - protein coats that enclose

and protect their nucleic acid.

– Each capsid is constructed from identical subunits

called capsomers made of protein.

– The capsid together with the nucleic acid are

nucleoscapsid.

– Some viruses have an external covering called

envelope; those lacking an envelope are naked

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General Structure of Viruses

• Two structural types:

– helical - continuous helix of capsomers

forming a cylindrical nucleocapsid

– icosahedral - 20-sided with 12 corners– vary in the number of capsomers

– Each capsomer may be made of 1 or several proteins.

– Some are enveloped.

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General Structure of Viruses

• Viral envelope

– mostly animal viruses

– acquired when the virus leaves the host cell

– exposed proteins on the outside of the envelope,

called spikes, essential for attachment of the virus

to the host cell

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Functions of Capsid/Envelope

• Protects the nucleic acid when the virion is

outside the host cell

• Helps to bind the virion to a cell surface and

assists the penetration of the viral DNA or

RNA into a suitable host cell

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General Structure of Viruses

• Complex viruses: atypical viruses

– Poxviruses lack a typical capsid and are

covered by a dense layer of lipoproteins.

– Some bacteriophages have a polyhedral

nucleocapsid along with a helical tail and

attachment fibers.

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Nucleic acids

• Viral genome – either DNA or RNA but

never both

• Carries genes necessary to invade host cell

and redirect cell’s activity to make new

viruses

• Number of genes varies for each type of

virus – few to hundreds

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Nucleic Acids

• DNA viruses

– usually double stranded (ds) but may be single stranded (ss)

– circular or linear

• RNA viruses

– usually single stranded, may be double stranded, may be segmented into separate RNA pieces

– ssRNA genomes ready for immediate translation are positive-sense RNA.

– ssRNA genomes that must be converted into proper form are negative-sense RNA.

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General Structure

• Pre-formed enzymes may be present.

– polymerases – DNA or RNA

– replicases – copy DNA

– reverse transcriptase –synthesis of DNA from

RNA (AIDS virus)

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How Viruses are Classified

• Main criteria presently used are structure,

chemical composition, and genetic makeup.

• No taxa above Family (no kingdom, phylum, etc.)

• Currently recognized: 3 orders, 63 families, and

263 genera of viruses

• Family name ends in -viridae, i.e.Herpesviridae

• Genus name ends in -virus, Simplexvirus

• Herpes simplex virus I (HSV-I)

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Modes of Viral Multiplication

General phases in animal virus multiplication cycle:

1. Adsorption - binding of virus to specific molecule on host cell

2. Penetration - genome enters host cell

3. Uncoating – the viral nucleic acid is released from the capsid

4. Synthesis – viral components are produced

5. Assembly – new viral particles are constructed

6. Release – assembled viruses are released by budding (exocytosis) or cell lysis

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Adsorption and Host Range

• Virus coincidentally collides with a susceptible

host cell and adsorbs specifically to receptor

sites on the cell membrane

• Spectrum of cells a virus can infect – host range

– hepatitis B – human liver cells

– poliovirus – primate intestinal and nerve cells

– rabies – various cells of many mammals

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Penetration/Uncoating

• Flexible cell membrane is penetrated by the

whole virus or its nucleic acid by:

– endocytosis – entire virus is engulfed and

enclosed in a vacuole or vesicle

– fusion – envelope merges directly with

membrane resulting in nucleocapsid’s entry

into cytoplasm

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Replication and Protein Production

• Varies depending on whether the virus is a DNA or RNA virus

• DNA viruses generally are replicated and assembled in the nucleus.

• RNA viruses generally are replicated and assembled in the cytoplasm.

– Positive-sense RNA contain the message for translation.

– Negative-sense RNA must be converted into positive-sense message.

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Release

• Assembled viruses leave host cell in one of two ways:

– budding – exocytosis; nucleocapsid binds to membrane which pinches off and sheds the viruses gradually; cell is not immediately destroyed

– lysis – nonenveloped and complex viruses released when cell dies and ruptures

• Number of viruses released is variable

– 3,000-4,000 released by poxvirus

– >100,000 released by poliovirus

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Damage to Host Cell

Cytopathic effects - virus-induced damage to cells

1. Changes in size & shape

2. Cytoplasmic inclusion bodies

3. Nuclear inclusion bodies

4. Cells fuse to form multinucleated cells.

5. Cell lysis

6. Alter DNA

7. Transform cells into cancerous cells

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Persistent Infections

• Persistent infections - cell harbors the virus and

is not immediately lysed

• Can last weeks or host’s lifetime; several can

periodically reactivate – chronic latent state

– measles virus – may remain hidden in brain cells for

many years

– herpes simplex virus – cold sores and genital herpes

– herpes zoster virus – chickenpox and shingles

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• Some animal viruses enter host cell and permanently

alter its genetic material resulting in cancer –

transformation of the cell.

• Transformed cells have increased rate of growth,

alterations in chromosomes, and capacity to divide for

indefinite time periods resulting in tumors.

• Mammalian viruses capable of initiating tumors are

called oncoviruses.

– Papillomavirus – cervical cancer

– Epstein-Barr virus – Burkitt’s lymphoma

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Multiplication Cycle in

Bacteriophages

• Bacteriophages – bacterial viruses (phages)

• Most widely studied are those that infect

Escherichia coli – complex structure, DNA

• Multiplication goes through similar stages as

animal viruses.

• Only the nucleic acid enters the cytoplasm -

uncoating is not necessary.

• Release is a result of cell lysis induced by viral

enzymes and accumulation of viruses - lytic cycle.

6 Steps in Phage Replication

1. Adsorption – binding of virus to specific

molecule on host cell

2. Penetration –genome enters host cell

3. Replication – viral components produced

4. Assembly - viral components assembled

5. Maturation – completion of viral formation

6. Release – viruses leave cell to infect other cells

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Lysogeny: The Silent Virus Infection

• Not all phages complete the lytic cycle.

• Some DNA phages, called temperate phages, undergo adsorption and penetration but don’t replicate.

• The viral genome inserts into bacterial genome and becomes an inactive prophage - the cell is not lysed.

• Prophage is retained and copied during normal cell division resulting in the transfer of temperate phage genome to all host cell progeny – lysogeny.

• Induction can occur resulting in activation of lysogenic prophage followed by viral replication and cell lysis.

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Lysogeny

• Lysogeny results in the spread of the virus without killing the host cell.

• Phage genes in the bacterial chromosome can cause the production of toxins or enzymes that cause pathology – lysogenic conversion.

– Corynebacterium diphtheriae

– Vibrio cholerae

– Clostridium botulinum

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Techniques in Cultivating and

Identifying Animal Viruses

• Obligate intracellular parasites that require appropriate cells to replicate

• Methods used:

– cell (tissue) cultures – cultured cells grow in sheets that support viral replication and permit observation for cytopathic effect

– bird embryos – incubating egg is an ideal system; virus is injected through the shell

– live animal inoculation – occasionally used when necessary

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Prions and Other Infectious Particles

Prions - misfolded proteins, contain no nucleic

acid

– cause transmissible spongiform encephalopathies –

fatal neurodegenerative diseases

– common in animals:• scrapie in sheep & goats

• bovine spongiform encephalopathies (BSE), aka mad cow disease

• wasting disease

• humans – Creutzfeldt-Jakob Syndrome (CJS)

• Extremely resistant to usual sterilization

techniques

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Other noncellular infectious agents

• Satellite viruses – dependent on other viruses

for replication

– adeno-associated virus – replicate only in cells

infected with adenovirus

– delta agent – naked strand of RNA expressed

only in the presence of hepatitis B virus

• Viroids - short pieces of RNA, no protein

coat; only been identified in plants, so far

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Detection and Treatment of Animal

Viral Infections

• More difficult than other agents

• Consider overall clinical picture

• Take appropriate sample

– Infect cell culture- look for characteristic cytopathic

effects

– Screen for parts of the virus

– Screen for immune response to virus (antibodies)

• Antiviral drugs can cause serious side effects