Endogenous retrovirus

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Dendrogram of various classes of endogenous retroviruses

Endogenous retroviruses (ERVs) are retroviruses derived from ancient viral infections of germ cells in humans, mammals and other vertebrates; as such their proviruses are passed on to the next generation and now remain in the genome. Retroviruses are viruses that reverse-transcribe their RNA into DNA for integration into the host's genome. Most retroviruses (such as HIV-1) infect somatic cells, but some can also infect germline cells (cells that make eggs and sperm) and once they have done so and have been transmitted to the next generation, they are termed endogenous. Endogenous retroviruses can persist in the genome of their host for long periods. However, they are generally only infectious for a short time after integration as they acquire 'knockout' mutations during host DNA replication. They can also be partially excised from the genome by a process known as recombinational deletion. They play a key role in evolution.^[1] Some Human ERVs have been implicated in certain autoimmune diseases and cancers.^[2][3]

Endosymbiotic ERVs in mammals

During pregnancy in viviparous mammals (all mammals except Monotremes), ERVs are activated and produced in high quantities during the implantation of the embryo. They are currently known to possess immunosuppressive properties, suggesting a role in protecting the embryo from its mother's immune system. Also viral fusion proteins apparently cause the formation of the placental syncytium^[4] in order to limit the exchange of migratory cells between the developing embryo and the body of the mother (something an epithelium will not do sufficiently, as certain blood cells are specialized to be able to insert themselves between adjacent epithelial cells). The immunodepressive action was the initial normal behavior of the virus, similar to HIV, the fusion proteins were a way to spread the infection to other cells by simply merging them with the infected one (HIV does this too). It is believed that the ancestors of modern viviparous mammals evolved after an infection by this virus, enabling the fetus to survive the immune system of the mother.^[5]

The human genome project found several thousand ERVs classified into 24 families.^[6]

Human endogenous retroviruses

Human endogenous retroviruses (HERVs) are suspected of involvement in some autoimmune diseases, in particular with multiple sclerosis. In this disease, there appears to be a specially associated member of the family of human endogenous retrovirus W known as "MS-associated retrovirus" (MSRV).^{[7] [8]}

Investigations also suggest possible HERV involvement in the HELLP syndrome and pre-eclampsia. There are many thousands of endogenous retroviruses within human DNA (HERVs comprise nearly 8% of the human genome, with 98,000 elements and fragments^[9]). All appear to be defective, containing nonsense mutations or major deletions, and cannot produce infectious virus particles. This is because most are just long-lasting traces of the original virus, having first integrated many millions of years ago. However, there is one family of viruses that have been active since the divergence of humans and chimpanzees. This family, termed HERV-K (HML2), makes up less than 1% of HERV elements but is one of the most studied. There are indications it has even been active in the past few hundred thousand years, as some human individuals carry more copies of the virus family than others. But the absence of known infectious members of the HERV-K(HML2) family, and the lack of elements with a full coding potential within the published human genome sequence, suggests that the family is less likely to be active at present.^[10]

Researchers are also looking at a possible link between HERVs and schizophrenia.^[11]

In 2006, researchers led by Thierry Heidmann at the Institut Gustave Roussy in Villejuif, France were able to recreate a HERV, which they dubbed Phoenix.^[12][13]

In 2007, a collaborative group lead by Doug Nixon and Keith Garrison at the University of California San Francisco, and by Mario Ostrowski and Brad Jones at the University of Toronto, published a study providing evidence for T cell immune responses against HERVs in human immunodeficiency virus (HIV) infected individuals.^[14] The group hypothesized that HIV induces HERV expression in HIV infected cells, and that a vaccine targeting HERV antigens could therefore specifically eliminate HIV infected cells. The potential advantage of this novel approach is that, by using HERV antigens as surrogate markers of HIV infected cells, it could circumvent the difficulty inherent in directly targeting notoriously diverse and rapidly mutating HIV antigens.

See also

• Bacteriophage
• Retrotransposon
• Germline
• Horizontal gene transfer

References

External links

• HERVd - human endogenous retrovirus database
• Retrosearch
• Löwer R, Löwer J, Kurth R (May 1996). "The viruses in all of us: characteristics and biological significance of human endogenous retrovirus sequences". Proc Natl Acad Sci USA. 93 (11): 5177–84. doi:10.1073/pnas.93.11.5177. PMID 8643549. PMC 39218. http://www.pnas.org/cgi/reprint/93/11/5177. 
• Molès JP, Tesniere A, Guilhou JJ (Jul 2005). "A new endogenous retroviral sequence is expressed in skin of patients with psoriasis". Br J Dermatol. 153 (1): 83–9. doi:10.1111/j.1365-2133.2005.06555.x. PMID 16029331. 
• Seifarth W, Frank O, Zeilfelder U, et al. (Jan 2005). "Comprehensive analysis of human endogenous retrovirus transcriptional activity in human tissues with a retrovirus-specific microarray". J Virol. 79 (1): 341–52. doi:10.1128/JVI.79.1.341-352.2005. PMID 15596828. 
• Knerr I, Beinder E, Rascher W (Feb 2002). "Syncytin, a novel human endogenous retroviral gene in human placenta: evidence for its dysregulation in preeclampsia and HELLP syndrome". Am J Obstet Gynecol. 186 (2): 210–3. doi:10.1067/mob.2002.119636. PMID 11854637. http://linkinghub.elsevier.com/retrieve/pii/S0002937802112282. 
• Gifford R, Tristem M (May 2003). "The evolution, distribution and diversity of endogenous retroviruses". Virus Genes 26 (3): 291–315. doi:10.1023/A:1024455415443. PMID 12876457. http://www.kluweronline.com/art.pdf?issn=0920-8569&volume=26&page=291.  Reprint PDF
• MeSH Endogenous+Retroviruses