ERV3 explained

HERV-R_7q21.2 provirus ancestral envelope (Env) polyprotein is a protein that in humans is encoded by the ERV3 gene.^{[1] [2]}

Function

The human genome includes many retroelements including the human endogenous retroviruses (HERVs), which compose about 7-8% of the human genome.^[3] ERV3, one of the most studied HERVs, is thought to have integrated 30 to 40 million years ago and is present in higher primates with the exception of gorillas. Taken together, the observation of genome conservation, the detection of transcript expression, and the presence of conserved ORFs is circumstantial evidence for a functional role. Similar endogenous retroviral Env genes like syncytin-1 have important roles in placental formation and embryonic development by enabling cell-cell fusion.^{[4] [5]} Despite its origin as an Env gene, ERV3 has a premature stop codon that precludes any cell-cell fusion functionality.^[6] However, it does have an immunosuppressive function that helps the fetus evade a damaging maternal immune response, which may explain its high expression in the placenta.^[7]

There is speculation that ERV3 originally did have cell-cell fusion functionality in the placenta, but that it was eventually supplanted by other Env genes like syncytin, leading to a loss of this function.^[8]

Another functional role is suggested by the observation that downregulation of ERV3 is reported in choriocarcinoma.^[9]

Further reading

• Sasaki T . [Integration and expression of human endogenous retrovirus] . [Hokkaido Igaku Zasshi] the Hokkaido Journal of Medical Science . 66 . 6 . 794–803 . November 1991 . 1783368 .
• Kato N, Pfeifer-Ohlsson S, Kato M, Larsson E, Rydnert J, Ohlsson R, Cohen M . Tissue-specific expression of human provirus ERV3 mRNA in human placenta: two of the three ERV3 mRNAs contain human cellular sequences . Journal of Virology . 61 . 7 . 2182–91 . July 1987 . 2884330 . 254242 . 10.1128/JVI.61.7.2182-2191.1987.
• Kato N, Larsson E, Cohen M . Absence of expression of a human endogenous retrovirus is correlated with choriocarcinoma . International Journal of Cancer . 41 . 3 . 380–5 . March 1988 . 3346101 . 10.1002/ijc.2910410310 . 46353425 .
• Cohen M, Kato N, Larsson E . ERV3 human endogenous provirus mRNAs are expressed in normal and malignant tissues and cells, but not in choriocarcinoma tumor cells . Journal of Cellular Biochemistry . 36 . 2 . 121–8 . February 1988 . 3356751 . 10.1002/jcb.240360203 . 24591624 .
• Cohen M, Powers M, O'Connell C, Kato N . The nucleotide sequence of the env gene from the human provirus ERV3 and isolation and characterization of an ERV3-specific cDNA . Virology . 147 . 2 . 449–58 . December 1985 . 3840930 . 10.1016/0042-6822(85)90147-3 .
• O'Connell CD, Cohen M . The long terminal repeat sequences of a novel human endogenous retrovirus . Science . 226 . 4679 . 1204–6 . December 1984 . 6505687 . 10.1126/science.6505687 . 1984Sci...226.1204O .
• Venables PJ, Brookes SM, Griffiths D, Weiss RA, Boyd MT . Abundance of an endogenous retroviral envelope protein in placental trophoblasts suggests a biological function . Virology . 211 . 2 . 589–92 . August 1995 . 7645262 . 10.1006/viro.1995.1442 . free .
• Larsson E, Andersson AC, Nilsson BO . Expression of an endogenous retrovirus (ERV3 HERV-R) in human reproductive and embryonic tissues--evidence for a function for envelope gene products . Upsala Journal of Medical Sciences . 99 . 2 . 113–20 . 1995 . 7716822 . 10.3109/03009739409179354 . free .
• Andersson AC, Merza M, Venables P, Pontén F, Sundström J, Cohen M, Larsson E . Elevated levels of the endogenous retrovirus ERV3 in human sebaceous glands . The Journal of Investigative Dermatology . 106 . 1 . 125–8 . January 1996 . 8592062 . 10.1111/1523-1747.ep12329612 . free .
• Larsson E, Venables P, Andersson AC, Fan W, Rigby S, Botling J, Oberg F, Cohen M, Nilsson K . Tissue and differentiation specific expression on the endogenous retrovirus ERV3 (HERV-R) in normal human tissues and during induced monocytic differentiation in the U-937 cell line . Leukemia . 11 . 142–4 . April 1997 . Suppl 3 . 9209323 .
• Sibata M, Ikeda H, Katumata K, Takeuchi K, Wakisaka A, Yoshoki T . Human endogenous retroviruses: expression in various organs in vivo and its regulation in vitro . Leukemia . 11 . 145–6 . April 1997 . Suppl 3 . 9209324 .
• Andersson AC, Svensson AC, Rolny C, Andersson G, Larsson E . Expression of human endogenous retrovirus ERV3 (HERV-R) mRNA in normal and neoplastic tissues . International Journal of Oncology . 12 . 2 . 309–13 . February 1998 . 9458354 . 10.3892/ijo.12.2.309 .
• de Parseval N, Heidmann T . Physiological knockout of the envelope gene of the single-copy ERV-3 human endogenous retrovirus in a fraction of the Caucasian population . Journal of Virology . 72 . 4 . 3442–5 . April 1998 . 9525678 . 109847 . 10.1128/JVI.72.4.3442-3445.1998.
• Rasmussen HB, Clausen J . Large number of polymorphic nucleotides and a termination codon in the env gene of the endogenous human retrovirus ERV3 . Disease Markers . 14 . 3 . 127–33 . November 1998 . 10427470 . 10.1155/1998/958379 . 3850859 . free .
• Lin L, Xu B, Rote NS . The cellular mechanism by which the human endogenous retrovirus ERV-3 env gene affects proliferation and differentiation in a human placental trophoblast model, BeWo . Placenta . 21 . 1 . 73–8 . January 2000 . 10692254 . 10.1053/plac.1999.0443 .
• Kim H, Crow TJ, Hyun BH . Assignment of the endogenous retrovirus HERV-R (ERV3) to human chromosome 7q11.2 by radiation hybrid mapping . Cytogenetics and Cell Genetics . 89 . 1–2 . 10 . 2000 . 10894926 . 10.1159/000015579 . 2024-07-25 . 85042388 .
• Andersson AC, Venables PJ, Tönjes RR, Scherer J, Eriksson L, Larsson E . Developmental expression of HERV-R (ERV3) and HERV-K in human tissue . Virology . 297 . 2 . 220–5 . June 2002 . 12083821 . 10.1006/viro.2002.1428 . free .

Notes and References

1. Kato N, Shimotohno K, VanLeeuwen D, Cohen M . Human proviral mRNAs down regulated in choriocarcinoma encode a zinc finger protein related to Krüppel . Molecular and Cellular Biology . 10 . 8 . 4401–5 . August 1990 . 2115127 . 361000 . 10.1128/mcb.10.8.4401.
2. O'Connell C, O'Brien S, Nash WG, Cohen M . ERV3, a full-length human endogenous provirus: chromosomal localization and evolutionary relationships . Virology . 138 . 2 . 225–35 . October 1984 . 6495650 . 10.1016/0042-6822(84)90347-7 .
3. Jern P, Coffin JM . 9254616 . Effects of retroviruses on host genome function . Annual Review of Genetics . 42 . 1 . 709–32 . December 2008 . 18694346 . 10.1146/annurev.genet.42.110807.091501 .
4. Vargas A, Moreau J, Landry S, LeBellego F, Toufaily C, Rassart E, Lafond J, Barbeau B . 6 . Syncytin-2 plays an important role in the fusion of human trophoblast cells . Journal of Molecular Biology . 392 . 2 . 301–18 . September 2009 . 19616006 . 10.1016/j.jmb.2009.07.025 .
5. Mallet F, Bouton O, Prudhomme S, Cheynet V, Oriol G, Bonnaud B, Lucotte G, Duret L, Mandrand B . 6 . The endogenous retroviral locus ERVWE1 is a bona fide gene involved in hominoid placental physiology . Proceedings of the National Academy of Sciences of the United States of America . 101 . 6 . 1731–6 . February 2004 . 14757826 . 341840 . 10.1073/pnas.0305763101 . 2004PNAS..101.1731M . free .
6. de Parseval N, Heidmann T . Physiological knockout of the envelope gene of the single-copy ERV-3 human endogenous retrovirus in a fraction of the Caucasian population . Journal of Virology . 72 . 4 . 3442–5 . April 1998 . 10.1128/JVI.72.4.3442-3445.1998 . 9525678 . 109847 .
7. Mangeney M, Renard M, Schlecht-Louf G, Bouallaga I, Heidmann O, Letzelter C, Richaud A, Ducos B, Heidmann T . 6 . Placental syncytins: Genetic disjunction between the fusogenic and immunosuppressive activity of retroviral envelope proteins . Proceedings of the National Academy of Sciences of the United States of America . 104 . 51 . 20534–9 . December 2007 . 18077339 . 2154466 . 10.1073/pnas.0707873105 . 2007PNAS..10420534M . free .
8. Chuong EB . Retroviruses facilitate the rapid evolution of the mammalian placenta . BioEssays . 35 . 10 . 853–61 . October 2013 . 23873343 . 4332834 . 10.1002/bies.201300059 .
9. Web site: Entrez Gene: ERV3 endogenous retroviral sequence 3 (includes zinc finger protein H-plk/HPF9).