Viruses
Viruses
VIRUSES
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VIRUSES
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General Characteristics of Viruses
They can infect animals, plants, bacteria (bacteriophages), fungi (mycophages) and protozoa.
Since viruses lack metabolic machinery, they cannot be grown in synthetic culture media.
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VIRUSES
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Size and Shapes of Viruses
Viruses are usually much smaller than bacteria and are submicroscopic. Most range in size
from 5 to 300 nm, although some Paramyxoviruses can be up to 14,000nm long.
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Animal DNA Viruses
Bacteriophages
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Size and Shapes of Viruses
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b. Polyhedral viruses consist of nucleic acid surrounded by a polyhedral (many-sided) shell
or capsid, usually in the form of an icosahedron
The subunits of the capsid are located
around the vertices or face of an
icosahedron. An icosahedron has 20
equilateral triangles arranged around the
face of a sphere. It is defined by having
2, 3 and 5 fold axis of symmetry.
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d. Binal (complex) viruses have neither helical nor polyhedral forms, are pleomorphic
(irregular shaped), or have complex structures
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Viral Structure
2. A capsid
nucleocapsid or naked viruses.
Attachment proteins project out from the capsid and bind the virus to susceptible host cells.
3. An envelope
The envelope may come from the host cell's nuclear membrane, vacuolar membranes
(packaged by the Golgi apparatus), or outer cytoplasmic membrane.
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Some bacteriophages are structurally much more complex than typical nucleocapsid or
enveloped viruses and may possess a unique tail structure composed of a base plate, tail
fibers, and a contractile sheath. Other bacteriophages, however, are simple icosahedrals or
helical.
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Classification and Origins of Viruses
Genera have the suffix virus. Within the Picornaviridae (transmitted via the faecal/oral and
airborne routes) there are 5 genera:
· enterovirus (alimentary tract) species e.g. poliovirus 1, 2, 3
· cardiovirus (neurotropic) species e.g. mengovirus
· rhinovirus (nasopharyngeal region) species e.g. Rhinovirus 1a
· hepatovirus (liver) species e.g. Hepatitits A virus 15
…
VIRUSES
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Viroids and Prions
Viroids are even more simple than viruses. They are small, circular, single-stranded molecules
of infectious RNA which has some double-stranded regions lacking even a protein coat.
They are the cause of a few plant diseases such as potato spindle-tuber disease, cucumber pale
fruit, citrus exocortis disease, and cadang-cadang (coconuts).
The structure of potato spindle tuber viroid (PSTVd) is indicated schematically below:
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Virusoids or satellite RNAs are also several hundred nucleotides long circular and single
stranded. They depend on a helper virus for replication. This helper virus also encapsidates
them. Virusoids replicate in cytoplasm using a RNA dependent RNA polymerase. This enzymic
activity is common in plants but not found in animal cells.
It is not known if viroids and virusoids are the progenitors of modern viruses or have
degenerated from other more complicated viruses. They can be spread by vegetative
propagation, within seeds or by direct inoculation either by insects or man.
There are similar infectious agents which infect humans. One such is the Hepatitis delta virus
(HDV).
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Viroids and Prions
Prions are infectious protein particles thought to be responsible for a group of transmissible
and/or inherited neurodegenerative diseases including Creutzfeldt-Jakob disease, kuru, and
Gerstmann-Straussler- syndrome in humans as well as scrapie in sheep and goats.
Most evidence indicates that the infectious prion proteins are modified forms of normal
proteins coded for by a host gene in the brain.
In scrapie and CJD, the normal prion protein has alpha-helices while in diseased animals it has
beta-sheets
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VIRUSES
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Life Cycle of Animal Viruses
Viruses that infect animal cells replicate by the productive life cycle.
Some viruses (HIV and herpes viruses) are able to become latent in certain cell types.
A few viruses increase the risk of certain cancers.
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The Productive Life Cycle of Animal Viruses
a.Attachment or adsorption
b. Penetration
c. Uncoating
d. Replication
e. Maturation
f. Release
g. Reinfection
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a. Attachment or adsorption
Adsorption involves the binding of attachment sites on the viral surface with receptor sites
on the host cell cytoplasmic membrane.
Attachment sites on the viral envelope Attachment sites on the viral capsid
bind to corresponding host cell receptors. bind to corresponding host cell receptors.
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b. Penetration
1. Enveloped viruses enter the host cell in one of two ways:
a. Fusion with the host cell cytoplasmic membrane and release of the nucleocapsid into the
cytoplasm.
Viral envelope fuses with host cell
Attachment sites on the virus membrane and nucleocapsid
bind to corresponding receptors enters the host cell
on the host cell membrane.
b. Endocytosis.
b. Endocytosis.
1. With enveloped viruses, the viral envelope is first removed either by fusing with the
cytoplasmic membrane during penetration, fusing with the membrane of the endocytic vesicle
after endocytosis, or fusing with the nuclear envelope of the host cell.
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c. Uncoating
In the case of naked viruses entering by endocytosis, the endocytic vesicle and the viral
capsid are enzymatically removed and the viral nucleic acid is released into the host cell's
cytoplasm.
The virus enters the host Endocytic vesicle and the viral The viral nucleic acid is released
cell by endocytosis. capsid are enzymatically removed into the host cell's cytoplasm.
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d. Replication
The viral genome directs the host cell's metabolic machinery (ribosomes, tRNA, nutrients,
energy, enzymes, etc.) to synthesize viral enzymes and viral parts.
The viral genome has to both replicate itself and become transcribed into viral mRNA
molecules. The viral mRNA can then be translated by the host cell into viral structural
components and enzymes need for replication and assembly of the virus.
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e. Maturation
The viral capsid assembles around the viral genome. Viral proteins and glycoproteins are
incorporated into the host cell's membranes.
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f. Release
2. With enveloped viruses, the host cell may or may not be lysed. The viruses obtain their
envelopes from host cell membranes by budding. Prior to budding, viral proteins and
glycoproteins are incorporated into the host cell's membranes.
Viruses obtaining their envelope from the cytoplasmic membrane are released during the
budding process. Those obtaining their envelopes from the membranes of the nucleus or the
Golgi apparatus are then released by exocytosis via transport vesicles
Budding
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Exocytosis
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g. Reinfection
Some viruses, capable of causing cell fusion, may be transported from one cell to adjacent cells
without being released, that is, they are transmitted by cell-to-cell contact whereby an infected
cell fuses with an uninfected cell.
Syncytia formation: The uninfected cells and infected cell fuse together forming a
multinucleated giant cell or syncytium 32
VIRUSES
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The Productive Life Cycle with Possible Latency
Some dsDNA animal viruses (herpes viruses, retroviruses) are able to remain latent within
infected host cells for long periods of time without replicating or causing harm.
Some of these viruses remain latent within the cytoplasm while others are able to insert or
integrate their DNA into the host cell's chromosomes. When the viral DNA is incorporated
into the host cell's DNA, it is called a provirus.
Viral latency is thought to result primarily from the lack of production of specific host cell
proteins that are required for the activation of the viral genes responsible for turning on
viral replication.
As long as these specific host cell proteins are not being made by the host cell, the virus can't
replicate. However, because the virus is inside the infected cell, it also can't be removed by the
body's immune responses and the person carries the virus throughout their life.
Subsequent activation of the host cell's DNA in response to extracellular stimuli, however,
can lead to synthesis of the specific host cell proteins required by the virus and these
proteins now activate the viral genes leading to a burst of viral replication via the productive
life cycle. 34
Herpes viruses, for example, are often latent in some cell types but productive in others.
In the case of HSV-1, HSV-2, and VZV, primary infection causes the virus to replicate within
epithelial cells. However, some of the viruses enter and migrate down neurons where they
become latent in the body of neurons. Subsequent activation of the latently infected neurons
by a variety of extracellular stimuli enables the viruses to migrate back up the nerve cell and
replicate again in the epithelial cells.
With EBV, the virus is productive in epithelial cells but latent in B-lymphocytes.
In the case of HIV, the viral genome eventually becomes a provirus. The provirus can directly
proceed into the productive life cycle and produce more virions or, when the specific host cell
proteins required for turning on the viral genes are not being produced by the host cell, it may
remain latent in the host cell's chromosomes.
Subsequent activation of the host cell by extracellular stimuli, however, causes the needed
proteins to be made and the virus replicates via the productive life cycle.
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VIRUSES
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VIRUSES
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The Role of Viruses in Tumor Production
Some viruses can play a role in converting normal host cells into tumor cells.
Hepatitis B virus (HBV), hepatitis C virus (HCV), human papilloma virus (HPV)…
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VIRUSES
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Life Cycle of Bacteriophages
There are two primary types of bacteriophages: lytic bacteriophages and temperate
bacteriophages.
1. Bacteriophages that replicate through the lytic life cycle are called lytic bacteriophages, and
are so named because they lyse the host bacterium as a normal part of their life cycle.
2. Bacteriophages capable of a lysogenic life cycle are termed temperate phages. When a
temperate phage infects a bacterium, it can either replicate by means of the lytic life cycle and
cause lysis of the host bacterium, or, it can incorporate its DNA into the bacterium's DNA and
become a noninfectious prophage.
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VIRUSES
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The Lytic Life Cycle of Lytic Bacteriophages
After infecting bacteria with lytic bacteriophages (DNA or RNA) in the lab, plaques can be
seen on the petri plates. Plaques are small clear areas on the agar surface where the host
bacteria have been lysed by lytic bacteriophages.
a. Adsorption
b. Penetration
c. Replication
d. Maturation
e. Release
f. Reinfection
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a. Adsorption
b. Penetration
Enzymes coded by the phage genome shut down the bacterium's macromolecular (protein, RNA,
DNA) synthesis. The phage replicates its genome and uses the bacterium's metabolic
machinery to synthesize phage enzymes and phage structural components.
d. Maturation
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Most of the phages (arrows) have assembled.
e. Release
f. Reinfection
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VIRUSES
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The Lysogenic Life Cycle
Bacteriophages (only DNA) capable of a lysogenic life cycle are termed temperate phages.
a. Adsorption
b. Penetration
OR
c. Replication
c. Prophage
formation d. Maturation
d. Maintaining e. Release
(Binary Fission)
e. Induction
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The adsorption (attachment to F pili of Gram-negative bacteria) and penetration steps are the
same as in the lytic life cycle.
c. Prophage formation
However, the phage does not shut down the host cell. Instead,
the phage DNA inserts or integrates into the host
bacterium's DNA. At this stage the virus is called a prophage.
Expression of the phage genes controlling phage replication is
blocked by a repressor protein, and the phage DNA replicates as
a part of the bacterium's DNA so that every daughter bacterium
now contains the prophage.
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Bacteriophage-Induced Alteration of Bacteria
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VIRUSES
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CONTROL OF VIRUSES
Since viruses lack the structures and metabolic processes that are altered by common
antibiotics, antibiotics are virtually useless in treating viral infections.
Amantadine and rimantidine are drugs that prevent influenza A viruses from the uncoating
step necessary for viral replication.
Zanamivir and oseltamivir are inhibitors of the influenza virus surface enzyme called
neuraminidase that is needed for release of newly formed influenza viruses from the infected
cell.
Most antiviral agents, however, work by inhibiting viral DNA synthesis (drugs chemically
resemble normal DNA nucleosides). They are selectively toxic because viral polymerases
are more prone to incorporate nucleotide analogs into their nucleic acid than are host cell
polymerases
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Current anti-HIV drugs include the following:
1. HIV nucleoside-analog (NA) reverse transcriptase inhibitors: most RT inhibitors are
NA. This prevents HIV provirus formation.
Zidovudine
Once zidovudine is
inserted into the growing
DNA strand being
transcribed from the viral
RNA by reverse
transcriptase, no further
nucleotides can be
attached
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2. HIV non-nucleoside reverse transcriptase inhibitors [e.g, nevirapine (Viramune)
delavirdine (Rescriptor), efavirenz (Sustiva)]
4. Agents interfering with the entry of HIV-1 into cells by inhibiting fusion of viral
envelopes with cellular membranes (e.g, enfuvirtide (Fuzeon) ).
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5. Certain cytokines are showing some success for viral infections.
None of the current antiviral agents kill and eliminate the viruses, they
simply inhibit their replication and decrease the severity of the disease.
In the case of some drugs, resistant virus strains are starting to emerge.
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MERCI
THANKS
&
GOOD
LUCK
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