Title: In 1898, Friedrich Loeffler and Paul Frosch found evidence that the cause of foot-and-mouth disease in livestock was an infectious particle smaller than any bacteria. This was the first clue to the nature of viruses, genetic entities that lie somewhere
1Introduction to the Viruses
In 1898, Friedrich Loeffler and Paul Frosch
found evidence that the cause of foot-and-mouth
disease in livestock was an infectious particle
smaller than any bacteria. This was the first
clue to the nature of viruses, genetic entities
that lie somewhere in the grey area between
living and non-living states. Viruses depend on
the host cells that they infect to reproduce.
When found outside of host cells, viruses exist
as a protein coat or capsid, sometimes enclosed
within a membrane. The capsid encloses either DNA
or RNA which codes for the virus elements. While
in this form outside the cell, the virus is
metabollically inert examples of such forms are
pictured below.
When it comes into contact with a host cell, a
virus can insert its genetic material into its
host, literally taking over the host's functions.
An infected cell produces more viral protein and
genetic material instead of its usual products.
Some viruses may remain dormant inside host cells
for long periods, causing no obvious change in
their host cells (a stage known as the lysogenic
phase). But when a dormant virus is stimulated,
it enters the lytic phase new viruses are
formed, self-assemble, and burst out of the host
cell, killing the cell and going on to infect
other cells. The diagram below at right shows a
virus that attacks bacteria, known as the lambda
bacteriophage, which measures roughly 200
nanometers.
2The origin of viruses is not known. Two theories
of viral origin1- Viruses may be derived from
DNA or RNA or from both nucleic acid components
of host cells that became able to replicate
autonomously and evolve independently.2-
Viruses may be degenerate forms of intracellular
parasites.
Evolutionary Origin of Viruses
Classification of VIRUSES
Viruses are separated into major groupings called
families on the basis of morphology, genome
structure, and replication. Virus families have
the suffix viridae-. Within each family,
subdivisions, called genera, are usually based on
physicochemical or serologic properties. Genus
names carry the suffix virus-. Subfamilies
virinae. In 1995, the international committee on
taxonomy of viruses had organized more than 4000
animal and plant viruses into 71 families, 11
subfamilies, and 164 genera, with hundreds of
viruses still unassigned. Currently 24 families
contain viruses that infect humans and animals.
According to the type of nucleic acid viruses
are classified into DNA and RNA viruses.
3Poxvirus Adenovirus
4DNA Viruses
A- Parvoviruses B- Polyomaviuses Formerly
part of Papovaviridae family before it splits
into 2 families. C- Papillomaviruses - Formerly
part of Papovaviridae family before it splits
into 2 families. D- Adenoviruses E-
Herpesviruses F- Poxviruses G- Hepadnaviruses
RNA Viruses
A- Picornaviruses
H- Reoviruses
O- Bornaviruses B- Flaviviruses
I-
Arboviruses P- Filoviruses C
Togaviruses
J- Arenaviruses
Q- Other viruses D- Coronaviruses
K- Bunyaviruses
R- Viroids E- Caliciviruses
L-
Orthomyxoviruses S- Prions F-
Retroviruses
M- Paramyxoviruses G- Astrovirses
N- Rhabdoviruses
5Virus Structure
Icosahedral symmetry
Complex symmetry
Helical symmetry
6Types of Symmetry
1- Icosahedral ( Cubic ) Symmetry 2- Helical
Symmetry 3- Complex Structure
Virus Structure
- Capsid protein shell that encloses the nucleic
acid. It is built of structure units. - STRUCTURE UNITS are the smallest functional
equivalent building units of the capsid. - CAPSOMERS are morphological units seen on the
surface of particles and represent clusters of
structure units. - The capsid together with its enclosed nucleic
acid is called the NUCLEOCAPSID. - The nucleocapsid may be invested in an ENVELOPE
which may contain material of host cell as well
as viral origin. - The VIRION is the complete infective virus
particle -
7 Cultivation of Viruses
Because viruses are unable to reproduce
independently of living cells, viruses cannot be
cultured in the same way as bacteria and
eucaryotic microbes. B) In the early years
animal viruses were cultivated in suitable host
animals or in embryonated eggs.
More recently, the animal viruses were able to
grown in cell culture. 1) Host cells are grown in
a petri dish or other container. A monolayer of
cells form2) The viruses are spread in the cells
and allowed to settle and attach3) A layer of
agar is overlayed on the cells.4) As the virus
replicates, cells lyse or become misshapened.
This results in plaques.
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9Reaction of Viruses to Physical and Chemical
Agents
1- Heat and Cold. 2- Stabilization of Viruses
by Salts. 3- pH. 4- Radiation. 5- Photodynamic
Inactivation. 6- Ether Susceptibility. 7-
Detergents. 8- Formaldehyde. 9- Antibiotics and
Other Antibacterial Agents.
10Replication of Viruses
Papova Virus Replication
General Steps in Viral Replication Cycle A-
Attachment B- Penetration C- Uncoating D-
Early transcription E- Early Translation F-
Nucleic acid synthesis G- Late transcription and
translation H- Assembly and release
11Influnza Virus Replication
12 Reovirus Replication
13Coronavirus
Influenzavirus
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15Pathogenesis and Control of Viral Diseases
More than 300 viruses are known to infect humans
and to cause as many as 50 different
syndromes. Steps in Viral Pathogenesis A- Viral
entry and primary replication. B- Viral Spread
and Cell Tropism. C- Cell Injury and Clinical
Illness. D- Recovery From Infection. E- Virus
Shedding. Host Immune Response 1- Both humeral
and cellular immunity are involved in control of
viral infection. 2- Mononuclear cells and
lymphocytes are involved in viral infection. 3-
The capsid serves as the targetfor the immune
response. 4- Cytotoxic T lymphocytes lyse virus
infected cells. 5- Secretory IgA antibody is
important against viral infections of the
respiratory or gastrointestinal tract. 6- Among
the nonimmune responses is the induction of
interferone.
16Adverse Effect of Certain Viruseson the Host
Immune Response
1- Some viruses infect and damage cells of the
immune system(AIDS). 2- Development of
pathologic changes and clinical illness. 3-
Immunopathologic disorder due to vaccine
immunization. 4- Development of
autoantibodies. Viruses have a variety of ways
that serve to suppress or evade the host immune
response and thus avoid eradication 1-
Oftentimes the viral proteins involved in
modulating the host response are not essential
for the growth of the virus. 2- Some viruses
infect cells of the immune system and abrogate
their function(AIDS). 3- They may infect neurons
that express little or no class 1
MHC(herpesviruses). 4- Form proteins that
inhibit MHC function(adenoviruses). 5- Viruses
may mutate and change the antigenic sites on
virion proteins(influenza virus). 6- Regulate
the level of viral surface proteins(herpesvirus).
17Viral Persistance Infections
Viral infections are usually self-limiting.
Sometimes, however, the virus persists for long
periods of time in the host. Long-term
virus-host interaction may take several forms 1-
Chronic infections. 2- Latent infections. 3-
Inapparent or subclinical infections. Acute
Viral Respiratory Infections. Viral Infections of
the Gastrointestinal Tract. Viral skin
Infections Viral Infections of the CNS Congenital
Viral Infections. Rubella, CMV, Herpes simplex,
Varicella-zoster, HBV, Enterovirus, HIV,
Parvovirus B19
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20Prevention and Treatment of Viral Infections
As bacteria and protozoa do not relay on host
cellular machinery for replication, so processes
specific to these organisms provide ready targets
for the development of antibacterial and
antiprotozoal drugs. However, because viruses
are obligate intracellular parasites, antiviral
drugs must be capable of selectively inhibiting
viral functions without damaging the host, making
the development of such drugs very difficult.
Furthermore an ideal drug would reduce disease
symptoms without modifying the viral infection so
much as to prevent an immune response in the
host. There is a need for antiviral drugs active
against viruses for which vaccines are not
available or not highly effective. A- Nucleoside
analogs. B- Nucleotide analogs. C-
Nonnucleoside Reverse transcriptase
inhibitors. D- Protease inhibitors
Saquinavir. E- Other types Amentadine,
Rimantadine, Foscarent, Methisazone. F-
Interferons Properties Synthesis
Antiviral activity and other biologic effects.
Clinical studies.
21Viral Vaccines
General Properties Killed Virus
Vaccines Advantages Disadvantages Attenuated
Live-Virus Vaccines Advantages Disadvantage Future
Prospects
22Simplified diagram of the Bacteriophage p22
virus. Original measures 995 pixels across
23- above) Ebola virus docks with cell membrane at
middle left. Viral RNA (yellow) is released into
the cytoplasm where it directs the production of
new viral proteins and genetic material. New
viral genomes are rapidly coated in protein to
create cores. These viral cores stack up in the
cell and migrate to the cell surface.
Transmembrane proteins (purple) are produced
which are ferried to the cell surface. Cores push
their way through the cell membrane becoming
enveloped in cell membrane and collecting their
transmembrane proteins (spikes) as they do so.
Examples of coiled virions are shown in the
background. -
24Simplified diagram of the Bacteriophage Lambda
showing combined lytic and lysogenic processes.
25Generalised scheme showing the ways that viruses
can enter animal cells. Some viruses can use more
than one strategy. Other means are also employed.
26SARS virion
27At left, a phage has attached to the LPS layer of
the bacterial cell wall. At right, the phage tail
has contracted and the phage DNA (red rope like
structure) is shown entering the cell.
Bacteriophage T4 virus attacking a bacterial cell
28Ways of Entrance of Viruses to Animal Cells
- . NAKED VIRUS - TRANSLOCATION particle crosses
cell membrane intact (cf Principles of Molecular
Virolgy, 3rd Edition, Alan J. Cann, Academic
Press p 117) - 2. NAKED VIRUS - GENOME INJECTION virus attaches
to cell surface and releases its genome which
penetrates the cytoplasm via a pore that has been
created in the plasma membrane. ( Bacteriophages,
which attack bacterial cells, also inject their
genomes and may use molecular "syringes" to do
so, please see our diagram of T4 phages
injecting. ) - 3. NAKED VIRUS - ENDOCYTOSIS virus attaches to
cell surface receptor molecules and sinks into a
clathrin coated pit. The pit invaginates and
finally closes off creating a clathrin coated
vesicle (drawn as a cage like sphere) and so the
contained virus particle is drawn into the
cytoplasm. The clathrin molecular cage soon
dissociates into component triskelions (the
propeller like objects) which leave a vesicle.
The resulting uncoated vesicle transports the
contained virion to an endosome. At some stage
thereafter, the viral components are released.
The virus shown in this example is an Adenovirus. - 4. ENVELOPED VIRUS - ENDOCYTOSIS MEMBRANE
FUSION virus enters cell by receptor mediated
endocytosis. The cell membrane merges (fuses)
with the endosome membrane and so the virus
components are released. The virus shown here is
an influenza virus, please see our Influenza
virus life cycle illustration . - 5. ENVELOPED VIRUS - MEMBRANE FUSION virus
enters the cell when its outer membrane fuses
with the plasma membrane at the cell surface. The
viral contents are then spilled into the
cytoplasm of the cell. This example is HIV, which
is unusual in having a conical core (most viral
cores tend to be more spherical). Please see our
HIV illustrations.
29- HIV attacks a macrophage (top middle) and a
Helper T Cell (lower left). New virus particles
then bud from the macrophage. A B-lymphocyte
(bottom right) gives rise to Plasma Cells
(reddish cells on right) that produce antibodies
(Y shaped molecules in red) that bind to HIV. A
killer cell (bottom middle) will attack virus
infected cells. The interaction of HIV and the
immune system is very complex and varies over
time. This image is available for licensing
worldwide. The -