Endogenous retrovirus

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Dendogram of various classes of endogenous retroviruses
Dendogram of various classes of endogenous retroviruses

Endogenous retroviruses are retroviruses derived from ancient 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. Many believe that they play a key role in evolution as well.

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[edit] 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 act as immunodepressors, protecting the embryo from its mother's immune system. Also viral fusion proteins apparently cause the formation of the placental syncytium 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 ERV is a virus similar to HIV (which causes AIDS in humans). 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 vivipary mammals evolved after an infection by this virus, enabling the fetus to survive the immune system of the mother. [1]

The human genome project found several thousand ERVs classified into 24 families.[2]

[edit] 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 familly of human endogenous retrovirus W known as "MS-associated retrovirus (MSRV).[3] [4].

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 8% of the human genome, with 98,000 elements and fragments[5]). 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.[6]

Researchers are also looking at a possible link between HERVs and schizophrenia.[7]

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.[8][9]

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[10]. 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.

[edit] References

  1. ^ Luis P. Villarreal. The Viruses That Make Us: A Role For Endogenous Retrovirus In The Evolution Of Placental Species. University of California, Irvine (lecture notes). Retrieved on 2008-02-03.
  2. ^ Luis P. Villarreal (October 2001). "Persisting Viruses Could Play Role in Driving Host Evolution". ASM News (American Society for Microbiology). 
  3. ^ Mameli G, Astone V, Arru G, Marconi S, Lovato L, Serra C, Sotgiu S, Bonetti B, Dolei A. (2007). "Brains and peripheral blood mononuclear cells of multiple sclerosis (MS) patients hyperexpress MS-associated retrovirus/HERV-W endogenous retrovirus, but not Human herpesvirus 6". PMID 17170460. 
  4. ^ Serra C, Mameli G, Arru G, Sotgiu S, Rosati G, Dolei A. (2003). "In vitro modulation of the multiple sclerosis (MS)-associated retrovirus by cytokines: implications for MS pathogenesis". PMID 14602576. 
  5. ^ Robert Belshaw; Pereira V; Katzourakis A; Talbot G; Paces J; Burt A; Tristem M. (April 2004). "Long-term reinfection of the human genome by endogenous retroviruses". Proc Natl Acad Sci U S A 101 (14): 4894–99. doi:10.1073/pnas.0307800101. PMID 15044706. 
  6. ^ Robert Belshaw; Anna L. A. Dawson; John Woolven-Allen; Joanna Redding; Austin Burt; Michael Tristem (Oct 2005). "Genomewide Screening Reveals High Levels of Insertional Polymorphism in the Human Endogenous Retrovirus Family HERV-K(HML2): Implications for Present-Day Activity". Journal of Virology 79 (19): 12507–14. doi:10.1128/JVI.79.19.12507-12514.2005. 
  7. ^ Yolken R. (Jun 2004). "Viruses and schizophrenia: a focus on herpes simplex virus.". Herpes Suppl 2:83A-88A. PMID 15319094. 
  8. ^ Martin Enserink (Nov 2006). "Viral Fossil Brought Back to Life". ScienceNOW Daily News. (news article)
  9. ^ Marie Dewannieux (2006). "Identification of an infectious progenitor for the multiple-copy HERV-K human endogenous retroelements" (abstract). Genome Research 16: 1548–1556. doi:10.1101/gr.5565706. PMID 17077319. (original paper)
  10. ^ Garrison KE*, Jones RB*, Meiklejohn DA, Anwar N, Ndhlovu LC, Chapman JM, Erickson AL, Agrawal A, Spotts G, Hecht FM, Rakoff-Nahoum S, Lenz J, Ostrowski MA, Nixon DF. T cell responses to human endogenous retroviruses in HIV-1 infection. PLoS Pathog. 2007 Nov;3(11):e165.*equal first-authors

[edit] See also

[edit] External links

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