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 play a key role in the evolution and ecology of Bacteria, Archaea, and Eukarya

• Viruses are obligate intracellular parasites

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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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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

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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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

• 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 RNA– 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

• 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 and shape2. Cytoplasmic inclusion bodies3. Inclusion bodies4. Cells fuse to form multinucleated cells5. 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 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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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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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