introduction to viruses 2

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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 tothe 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 lambdabacteriophage, which measures roughly 200 nanometers.



The origin of viruses is not known. Two theories of viral origin:

1- 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.

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.



Poxvirus Adenovirus



A- ParvovirusesB- 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

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



Helical symmetry

Icosahedral symmetry Complex symmetry



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

1- Icosahedral ( Cubic ) Symmetry

2- Helical Symmetry

3- Complex Structure



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 inembryonated 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 form

2) The viruses are spread in the cells and allowed to settle and attach

3) A layer of agar is overlayed on the cells.

4) As the virus replicates, cells lyse or become misshapened. This results in plaques.



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.



General Steps in Viral Replication Cycle

A- Attachment

B- PenetrationC- Uncoating

D- Early transcription

E- Early Translation

F- Nucleic acid synthesis

G- Late transcription and translation

H- Assembly and release



Coronavirus Influenzavirus



More than 300 viruses are known to infect humans and to cause as many as 50 different syndromes.

Steps in Viral PathogenesisA- 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.



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).



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 andantiprotozoal 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.



General Properties

Killed ± Virus Vaccines

Advantages

Disadvantages

Attenuated Live-Virus Vaccines

Advantages

Disadvantage

Future Prospects



Simplified diagram of the Bacteriophage p22 virus. Original measures

995 pixels across



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 inthe background.



Simplified diagram of the Bacteriophage Lambda showing combined lytic and lysogenic processes.



Generalised scheme showing the ways that viruses can enter animal cells. Some viruses can use more than one strategy.

Other means are also employed.



SARS virion



Bacteriophage T4

virus attacking a

bacterial cell

At 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 shownentering the cell.



. NAKED VIRUS - TR ANSLOCATION: particle crosses cell membrane intact (cf Principles of Molecular Virolgy, 3rd Edition, Alan J. Cann, Academic Press p 117)

2. NAKED VIRUS -G

ENOME INJECTION: virus attaches to cell surface andreleases its genome which penetrates the cytoplasm via a pore that has been created inthe 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 dissociatesinto component triskelions (the propeller like objects) which leave a vesicle. Theresulting uncoated vesicle transports the contained virion to an endosome. At some stagethereafter, the viral components are released. The virus shown in this example is anAdenovirus.

4. ENVELOPED VIRUS - ENDOCYTOSIS & MEMBR ANE FUSION: virus enterscell by receptor mediated endocytosis. The cell membrane merges (fuses) with the

endosome membrane and so the virus components are released. The virus shown here isan influenza virus, please see our Influenza virus life cycle illustration .

5. ENVELOPED VIRUS - MEMBR ANE FUSION: virus enters the cell when itsouter membrane fuses with the plasma membrane at the cell surface. The viral contentsare then spilled into the cytoplasm of the cell. This example is HIV, which is unusual inhaving a conical core (most viral cores tend to be more spherical). Please see our HIVillustrations.



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

introduction to viruses 2

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