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Virology

Virology is the study of viruses – submicroscopic, parasitic particles of genetic material contained in a protein coat – and virus-like agents. It focuses on the following aspects of viruses: their structure, classification and evolution, their ways to infect and exploit host cells for reproduction, their interaction with host organism physiology and immunity, the diseases they cause, the techniques to isolate and culture them, and their use in research and therapy. Virology is considered to be a subfield of microbiology or of medicine.


Virus structure and classification
A major branch of virology is virus classification. Viruses can be classified according to the host cell they infect: animal viruses, plant viruses, fungal viruses, and bacteriophages (viruses infecting bacteria, which include the most complex viruses). Another classification uses the geometrical shape of their capsid (often a helix or an icosahedron) or the virus's structure (e.g. presence or absence of a lipid envelope). Viruses range in size from about 30 nm to about 450 nm, which means that most of them cannot be seen with light microscopes. The shape and structure of viruses has been studied by electron microscopy, NMR spectroscopy, and X-ray crystallography.

The most useful and most widely used classification system distinguishes viruses according to the type of nucleic acid they use as genetic material and the viral replication method they employ to coax host cells into producing more viruses:

    DNA viruses (divided into double-stranded DNA viruses and single-stranded DNA viruses),
    RNA viruses (divided into positive-sense single-stranded RNA viruses, negative-sense single-stranded RNA viruses and the much less common double-stranded RNA viruses),
    reverse transcribing viruses (double-stranded reverse-transcribing DNA viruses and single-stranded reverse-transcribing RNA viruses including retroviruses).

The latest report by the International Committee on Taxonomy of Viruses (2005) lists 5450 viruses, organized in over 2,000 species, 287 genera, 73 families and 3 orders.

Virologists also study subviral particles, infectious entities notably smaller and simpler than viruses:

    viroids (naked circular RNA molecules infecting plants),
    satellites (nucleic acid molecules with or without a capsid that require a helper virus for infection and reproduction), and
    prions (proteins that can exist in a pathological conformation that induces other prion molecules to assume that same conformation).

Taxa in virology are not necessarily monophyletic, as the evolutionary relationships of the various virus groups remain unclear. Three hypotheses regarding their origin exist:

    Viruses arose from non-living matter, separately from yet in parallel to cells, perhaps in the form of self-replicating RNA ribozymes similar to viroids.
    Viruses arose by genome reduction from earlier, more competent cellular life forms that became parasites to host cells and subsequently lost most of their functionality; examples of such tiny parasitic prokaryotes are Mycoplasma and Nanoarchaea.
    Viruses arose from mobile genetic elements of cells (such as transposons, retrotransposons or plasmids) that became encapsulated in protein capsids, acquired the ability to "break free" from the host cell and infect other cells.

Of particular interest here is mimivirus, a giant virus that infects amoebae and encodes much of the molecular machinery traditionally associated with bacteria. Is it a simplified version of a parasitic prokaryote, or did it originate as a simpler virus that acquired genes from its host?

The evolution of viruses, which often occurs in concert with the evolution of their hosts, is studied in the field of viral evolution.

While viruses reproduce and evolve, they do not engage in metabolism, do not move, and depend on a host cell for reproduction. The often-debated question of whether they are alive or not is a matter of definition that does not affect the biological reality of viruses.

Viral diseases and host defenses
One main motivation for the study of viruses is the fact that they cause many important infectious diseases, among them the common cold, influenza, rabies, measles, many forms of diarrhea, hepatitis, Dengue fever, yellow fever, polio, smallpox and AIDS. Herpes simplex causes cold sores and genital herpes and is under investigation as a possible factor in Alzheimer's.

Some viruses, known as oncoviruses, contribute to the development of certain forms of cancer. The best studied example is the association between Human papillomavirus and cervical cancer: almost all cases of cervical cancer are caused by certain strains of this sexually transmitted virus. Another example is the association of infection with hepatitis B and hepatitis C viruses and liver cancer.

Some subviral particles also cause disease: the transmissible spongiform encephalopathies, which include Kuru, Creutzfeldt-Jakob disease and bovine spongiform encephalopathy ("mad cow disease"), are caused by prions., hepatitis D is due to a satellite virus.

The study of the manner in which viruses cause disease is viral pathogenesis. The degree to which a virus causes disease is its virulence.

When the immune system of a vertebrate encounters a virus, it may produce specific antibodies which bind to the virus and neutralize its infectivity or mark it for destruction. Antibody presence in blood serum is often used to determine whether a person has been exposed to a given virus in the past, with tests such as ELISA. Vaccinations protect against viral diseases, in part, by eliciting the production of antibodies. Monoclonal antibodies, specific to the virus, are also used for detection, as in fluorescence microscopy.

A second defense of vertebrates against viruses, cell-mediated immunity, involves immune cells known as T cells: the body's cells constantly display short fragments of their proteins on the cell's surface, and if a T cell recognizes a suspicious viral fragment there, the host cell is destroyed and the virus-specific T-cells proliferate. This mechanism is jump-started by certain vaccinations.

RNA interference, an important cellular mechanism found in plants, animals and many other eukaryotes, most likely evolved as a defense against viruses. An elaborate machinery of interacting enzymes detects double-stranded RNA molecules (which occur as part of the life cycle of many viruses) and then proceeds to destroy all single-stranded versions of those detected RNA molecules.

Every lethal viral disease presents a paradox: killing its host is obviously of no benefit to the virus, so how and why did it evolve to do so? Today it is believed that most viruses are relatively benign in their natural hosts; some viral infection might even be beneficial to the host. The lethal viral diseases are believed to have resulted from an "accidental" jump of the virus from a species in which it is benign to a new one that is not accustomed to it (see zoonosis). For example, viruses that cause serious influenza in humans probably have pigs or birds as their natural host, and HIV is thought to derive from the benign non-human primate virus SIV.

While it has been possible to prevent (certain) viral diseases by vaccination for a long time, the development of antiviral drugs to treat viral diseases is a comparatively recent development. The first such drug was interferon, a substance that is naturally produced when an infection is detected and stimulates other parts of the immune system.

Molecular biology research and viral therapy
Bacteriophages, the viruses which infect bacteria, can be relatively easily grown as viral plaques on bacterial cultures. Bacteriophages occasionally move genetic material from one bacterial cell to another in a process known as transduction, and this horizontal gene transfer is one reason why they served as a major research tool in the early development of molecular biology. The genetic code, the function of ribozymes, the first recombinant DNA and early genetic libraries were all arrived at using bacteriophages. Certain genetic elements derived from viruses, such as highly effective promoters, are commonly used in molecular biology research today.

Growing animal viruses outside of the living host animal is more difficult. Classically, fertilized chicken eggs have often been used, but cell cultures are increasingly employed for this purpose today.

Since some viruses that infect eukaryotes need to transport their genetic material into the host cell's nucleus, they are attractive tools for introducing new genes into the host (known as transformation or transfection). Modified retroviruses are often used for this purpose, as they integrate their genes into the host's chromosomes.

This approach of using viruses as gene vectors is being pursued in the gene therapy of genetic diseases. An obvious problem to be overcome in viral gene therapy is the rejection of the transforming virus by the immune system.

Phage therapy, the use of bacteriophages to combat bacterial diseases, was a popular research topic before the advent of antibiotics and has recently seen renewed interest.

Oncolytic viruses are viruses that preferably infect cancer cells. While early efforts to employ these viruses in the therapy of cancer failed, there have been reports in 2005 and 2006 of encouraging preliminary results.

Other uses of viruses
A new application of genetically engineered viruses in nanotechnology was recently described; see the uses of viruses in material science and nanotechnology. For a use in mapping neurons see the applications of pseudorabies in neuroscience.

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