Endogenous retrovirus

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.

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 [S. Mi "et al.", [http://www.ncbi.nlm.nih.gov/pubmed/10693809?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus "Syncytin is a captive retroviral envelope protein involved in human placental morphogenesis"] , Nature, 403, 785-9, Feb. 17, 2000.] 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 viviparous mammals evolved after an infection by this virus, enabling the fetus to survive the immune system of the mother. [cite web
url= http://www.dbc.uci.edu/~faculty/villarreal/new1/erv-placental.html
title= The Viruses That Make Us: A Role For Endogenous Retrovirus In The Evolution Of Placental Species
author = Luis P. Villarreal
publisher = University of California, Irvine (lecture notes)
accessdate = 2008-02-03 ]

The human genome project found several thousand ERVs classified into 24 families. [cite journal
url=http://newsarchive.asm.org/oct01/feature1.asp
title= Persisting Viruses Could Play Role in Driving Host Evolution
author = Luis P. Villarreal
journal = ASM News (American Society for Microbiology)
month = October | year = 2001]

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). [cite journal
author=Mameli G, Astone V, Arru G, Marconi S, Lovato L, Serra C, Sotgiu S, Bonetti B, Dolei A.
year=2007
url=
title=Brains and peripheral blood mononuclear cells of multiple sclerosis (MS) patients hyperexpress MS-associated retrovirus/HERV-W endogenous retrovirus, but not Human herpesvirus 6
month=
volume=
issue=
pages=
pmid=17170460] [cite journal
author=Serra C, Mameli G, Arru G, Sotgiu S, Rosati G, Dolei A.
year=2003
url=
title=In vitro modulation of the multiple sclerosis (MS)-associated retrovirus by cytokines: implications for MS pathogenesis
month=
volume=
issue=
pages=
pmid=14602576] .

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 [cite journal
author=Robert Belshaw
coauthors=Pereira V; Katzourakis A; Talbot G; Paces J; Burt A; Tristem M.
year=2004
url=http://www.pubmedcentral.com/articlerender.fcgi?artid=387345
title=Long-term reinfection of the human genome by endogenous retroviruses |journal=Proc Natl Acad Sci U S A
month=April
volume=101
issue=14
pages=4894–99
pmid=15044706
doi=10.1073/pnas.0307800101 ] ). 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. [cite journal
author=Robert Belshaw
coauthors=Anna L. A. Dawson; John Woolven-Allen; Joanna Redding; Austin Burt; Michael Tristem
year=2005
url=http://jvi.asm.org/cgi/content/full/79/19/12507
title=Genomewide Screening Reveals High Levels of Insertional Polymorphism in the Human Endogenous Retrovirus Family HERV-K(HML2): Implications for Present-Day Activity
journal=Journal of Virology
month=Oct
pages=12507–14
volume=79
issue=19
pmid=
doi=10.1128/JVI.79.19.12507-12514.2005]

Researchers are also looking at a possible link between HERVs and schizophrenia. [cite journal
journal=Herpes Suppl 2:83A-88A
year=2004
month=Jun
title=Viruses and schizophrenia: a focus on herpes simplex virus.
url= http://www.stanleylab.org/publications/VIRUSES.asp
author=Yolken R.
pmid=15319094 ]

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. [cite journal
author=Martin Enserink
year=2006
month=Nov
url=http://sciencenow.sciencemag.org/cgi/content/full/2006/1101/4
title=Viral Fossil Brought Back to Life
journal=ScienceNOW Daily News(news article)] [cite journal
journal = Genome Research
title = Identification of an infectious progenitor for the multiple-copy HERV-K human endogenous retroelements
url = http://www.genome.org/cgi/content/abstract/16/12/1548
author = Marie Dewannieux
coauthor = Francis Harper, Aurélien Richaud, Claire Letzelter, David Ribet, Gérard Pierron, and Thierry Heidmann
volume = 16
year = 2006
pmid = 17077319
pages=1548–1556
doi = 10.1101/gr.5565706
format = abstract(original paper)]

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 [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 ] . 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.

References

ee also

*Phage
*Retrotransposon
*Germline
*Horizontal gene transfer

External links

* [http://herv.img.cas.cz/ HERVd - human endogenous retrovirus database]
* [http://www.retrosearch.dk Retrosearch]
*Roswitha Löwer, Johannes Löwer, Reinhard Kurth, (1996). [http://www.pnas.org/cgi/reprint/93/11/5177 "The viruses in all of us: Characteristics and biological significance of human endogenous retrovirus sequences"] "Proceedings of the National Academy of Sciences". 93:5177-5184
*Moles JP, Tesniere A, Guilhou JJ. [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16029331&query_hl=4 "A new endogenous retroviral sequence is expressed in skin of patients with psoriasis."] "British Journal of Dermatology". 2005 Jul;153(1):83-9.
*Seifarth W, Frank O, Zeilfelder U, Spiess B, Greenwood AD, Hehlmann R, Leib-Mosch C. [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15596828&query_hl=4 "Comprehensive analysis of human endogenous retrovirus transcriptional activity in human tissues with a retrovirus-specific microarray."] "Journal of Virology". 2005 Jan;79(1):341-352.
*Knerr I, Beinder E, Rascher W. [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11854637&query_hl=6 "Syncytin, a novel human endogenous retroviral gene in human placenta: evidence for its dysregulation in preeclampsia and HELLP syndrome."] "American Journal of Obstestrics and Gynecolology". 2002 Feb;186(2):210-213.
*Gifford R, Tristem M. [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12876457&query_hl=16 "The evolution, distribution and diversity of endogenous retroviruses."] "Virus Genes". 2003 May;26(3):291-315. [http://www.vgb.ucl.ac.uk/pdf/Gifford_2003.pdf]
*MeshName|Endogenous+Retroviruses