viruses

Prof. Dr Wael Abbas Elnaggar PhD

Dr. Samreen Soomro PhD
Department of Basic Health Science
Faculty of Pharmacy, NBU

Assigned Reading:

Foundations in Microbiology, Ninth Edition - Talaro,

Chess
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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.

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 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