Retrovirus

Retroviruses
Virus classification
Group: Group VI (ssRNA-RT) Family: Retroviridae
Genera
Subfamily: Orthoretrovirinae Alpharetrovirus Betaretrovirus Gammaretrovirus Deltaretrovirus Epsilonretrovirus Lentivirus Subfamily: Spumaretrovirinae Spumavirus

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

A retrovirus is any virus belonging to the viral family Retroviridae. They are enveloped viruses possessing an RNA genome, and replicate via a DNA intermediate. Retroviruses rely on the enzyme reverse transcriptase to perform the reverse transcription of its genome from RNA into DNA, which can then be integrated into the host's genome with an integrase enzyme. The virus then replicates as part of the cell's DNA.

Description of virus

The virus itself stores its nucleic acid, in the form of a +mRNA (including the 5'cap and 3'PolyA inside the virion) genome and serves as a means of delivery of that genome into cells it targets as an obligate parasite, and constitutes the infection. Once in the host's cell, the RNA strands undergo reverse transcription in the cytosol and are integrated into the host's genome, at which point the retroviral DNA is referred to as a provirus.

Multiplication

When retroviruses have integrated their own genome into the germ line, their genome is passed on to a following generation. These endogenous retroviruses, contrasted with exogenous ones, now make up 5-8% of the human genome. Most insertions have no known function and are often referred to as "junk DNA". However, many endogenous retroviruses play important roles in host biology, such as control of gene transcription, cell fusion during placental development in the course of the germination of an embryo, and resistance to exogenous retroviral infection. Endogenous retroviruses have also received special attention in the research of immunology-related pathologies, such as autoimmune diseases like multiple sclerosis, although endogenous retroviruses have not yet been proven to play any causal role in this class of disease. The role of endogenous retroviruses in human gene evolution is explored in a 2005 peer-reviewed article.

While transcription was classically thought to only occur from DNA to RNA, reverse transcriptase transcribes RNA into DNA. The term "retro" in retrovirus refers to this reversal (making DNA from RNA) of the central dogma of molecular biology. Reverse transcriptase activity outside of retroviruses has been found in almost all eukaryotes, enabling the generation and insertion of new copies of retrotransposons into the host genome. It is important to note that a retrovirus must "bring" its own reverse transcriptase in its capsid, otherwise it is unable to utilize the infected cell's enzymes to carry out the task, due to the unusual nature of producing DNA from RNA.

Because reverse transcription lacks the usual proofreading of DNA replication, this kind of virus mutates very often. This enables the virus to grow resistant to antiviral pharmaceuticals quickly, and impedes, for example, the development of an effective vaccine against the retrovirus HIV.

Genes

Retrovirus genomes commonly contain these three open reading frames that encode for proteins that can be found in the mature virus:

• group-specific antigen (gag) codes for core and structural proteins of the virus;
• polymerase (pol) codes for reverse transcriptase, protease and integrase; and,
• envelope (env) codes for the retroviral coat proteins.

Provirus

This DNA can be incoporated into host genome as a provirus that can be passed on to progeny cells. In this way some of retroviruses can convert normal cells into cancer cells.

Development of retroviruses

Studies of retroviruses led to the first demonstrated synthesis of DNA from RNA templates, a fundamental mode for transferring genetic material that occurs in both eukaryotes and prokaryotes.

It has been speculated that the RNA to DNA transcription processes used by retroviruses may have first caused DNA to be used as genetic material.

In this model, the RNA world hypothesis, cellular organisms adopted the more chemically stable DNA when retroviruses evolved to create DNA from the RNA templates.

Classification

Exogenous

The following genera are included here:

• Genus Alpharetrovirus; type species: Avian leukosis virus
• Genus Betaretrovirus; type species: Mouse mammary tumour virus
• Genus Gammaretrovirus; type species: Murine leukemia virus; others include Feline leukemia virus
• Genus Deltaretrovirus; type species: Bovine leukemia virus; others include the cancer-causing Human T-lymphotropic virus
• Genus Epsilonretrovirus; type species: Walleye dermal sarcoma virus
• Genus Lentivirus; type species: Human immunodeficiency virus 1; others include Simian, Feline immunodeficiency viruses
• Genus Spumavirus; type species: Chimpanzee foamy virus

These were previously divided into three subfamilies (Oncovirinae, Lentivirinae, and Spumavirinae), but with current knowledge of retroviruses, this is no longer appropriate. (The term oncovirus is still commonly used, though.)

Endogenous

Main article: endogenous retrovirus

Endogenous retroviruses are not formally included in this classification system, and are broadly classified into three classes, on the basis of relatedness to exogenous genera:

• Class I are most similar to the gammaretroviruses
• Class II are most similar to the betaretroviruses and alpharetroviruses
• Class III are most similar to the spumaviruses

Treatment

Main article: Antiretroviral drug

Antiretroviral drugs are medications for the treatment of infection by retroviruses, primarily HIV. Different classes of antiretroviral drugs act at different stages of the HIV life cycle. Combination of several (typically three or four) antiretroviral drugs is known as Highly Active Anti-Retroviral Therapy (HAART).

Genetic barrier

The genetic barrier is loosely defined as the difficulty for retroviruses to evade antiretroviral drugs by mutating into resistant types.

External links

• Retrovirology Scientific journal
• Retroviruses at rcn.com
• NCBI retrovirus book online
• Annals of Science: Darwin’s Surprise, New Yorker Dec 3 2007