Foundations in

Microbiology Seventh Edition

Chapter 6

An Introduction

to Viruses

Lecture PowerPoint to accompany

Talaro

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6.1 The Search for the Elusive Virus

• Louis Pasteur postulated that rabies was

caused by a virus (1884)

• Ivanovski and Beijerinck showed a disease

in tobacco was caused by a virus (1890s)

• 1950s virology was a multifaceted

discipline

– Viruses: noncellular particles with a definite

size, shape, and chemical composition

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6.2 The Position of Viruses in the

Biological Spectrum

• There is no universal agreement on how and

when viruses originated

• Viruses are considered the most abundant

microbes on earth

• Viruses played a role in evolution of

Bacteria, Archaea, and Eukarya

• Viruses are obligate intracellular parasites

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6.3 General Structure of Viruses • Size range –

– most <0.2 μm; requires electron microscope

Viral Components: Capsids, Nucleic

Acids, and Envelopes

• Viruses bear no resemblance to cells

– Lack protein-synthesizing machinery

• Viruses contain only the parts needed to

invade and control a host cell

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General Structure of Viruses

• Capsids

– All viruses have capsids - protein coats that enclose

and protect their nucleic acid

– The capsid together with the nucleic acid are

nucleocapsid

– Some viruses have an external covering called

envelope; those lacking an envelope are naked

– Each capsid is constructed from identical subunits

called capsomers made of protein

Figure 6.4 Structure of Virus

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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

Helical Nucleocapsids

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Figure 6.7 Figure 6.8

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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 virus is

outside the host cell

• Helps the virus to bind 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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Figure 6.9

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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 RNA

– Reverse transcriptase – synthesis of DNA from

RNA (AIDS virus)

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6.4 How Viruses Are Classified

• Main criteria presently used are structure,

chemical composition, and genetic makeup

• 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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6.5 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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Figure 6.12

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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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Figure 6.13

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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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Figure 6.15

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Damage to Host Cell

Cytopathic effects - virus-induced damage to cells

1. Changes in size and shape

2. Cytoplasmic inclusion bodies

3. 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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Figure 6.16

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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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Figure 6.17

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Figure 6.18

Figure 6.19

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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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Figure 6.17

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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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6.6 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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Figure 6.20

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Figure 6.21

6.7 Medical Importance of Viruses

• Viruses are the most common cause of

acute infections

• Several billion viral infections per year

• Some viruses have high mortality rates

• Possible connection of viruses to chronic

afflictions of unknown cause

• Viruses are major participants in the earth’s

ecosystem

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6.8 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 and goats

• Bovine spongiform encephalopathies (BSE), a.k.a. mad cow disease

• Wasting disease in elk

• Humans – Creutzfeldt-Jakob Syndrome (CJS)

• Extremely resistant to usual sterilization

techniques

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Figure 6.22

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Other Noncellular Infectious Agents

• Satellite viruses – dependent on other viruses

for replication

– Adeno-associated virus – replicates 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

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6.9 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