Foundations in Microbiology

Sixth Edition

Chapter 6An Introduction to the

Viruses

Lecture PowerPoint to accompany

Talaro

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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 MultiplicationGeneral phases in animal virus multiplication

cycle:1. Adsorption - binding of virus to specific

molecule on host cell2. Penetration - genome enters host cell3. Uncoating – the viral nucleic acid is released

from the capsid4. Synthesis – viral components are produced5. Assembly – new viral particles are constructed6. 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 & shape2. Cytoplasmic inclusion bodies3. Nuclear inclusion bodies4. Cells fuse to form multinucleated cells.5. Cell lysis6. Alter DNA7. 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 Replication1. Adsorption – binding of virus to specific

molecule on host cell2. Penetration –genome enters host cell3. Replication – viral components produced4. Assembly - viral components assembled5. Maturation – completion of viral formation6. 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