The human genome includes many retroelements including the human endogenous retroviruses (HERVs), which compose about 7-8% of the human genome.[6] 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.[7][8] Despite its origin as an Env gene, ERV3 has a premature stop codon that precludes any cell-cell fusion functionality.[9] 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.[10]
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.[11]
Another functional role is suggested by the observation that downregulation of ERV3 is reported in choriocarcinoma.[5]
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Sasaki T (November 1991). "[Integration and expression of human endogenous retrovirus]". [Hokkaido Igaku Zasshi] the Hokkaido Journal of Medical Science. 66 (6): 794–803. PMID1783368.
Kato N, Larsson E, Cohen M (March 1988). "Absence of expression of a human endogenous retrovirus is correlated with choriocarcinoma". International Journal of Cancer. 41 (3): 380–5. doi:10.1002/ijc.2910410310. PMID3346101. S2CID46353425.
Cohen M, Kato N, Larsson E (February 1988). "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. doi:10.1002/jcb.240360203. PMID3356751. S2CID24591624.
O'Connell CD, Cohen M (December 1984). "The long terminal repeat sequences of a novel human endogenous retrovirus". Science. 226 (4679): 1204–6. Bibcode:1984Sci...226.1204O. doi:10.1126/science.6505687. PMID6505687.
Larsson E, Venables P, Andersson AC, Fan W, Rigby S, Botling J, Oberg F, Cohen M, Nilsson K (April 1997). "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 Suppl 3: 142–4. PMID9209323.
Sibata M, Ikeda H, Katumata K, Takeuchi K, Wakisaka A, Yoshoki T (April 1997). "Human endogenous retroviruses: expression in various organs in vivo and its regulation in vitro". Leukemia. 11 Suppl 3: 145–6. PMID9209324.
Andersson AC, Svensson AC, Rolny C, Andersson G, Larsson E (February 1998). "Expression of human endogenous retrovirus ERV3 (HERV-R) mRNA in normal and neoplastic tissues". International Journal of Oncology. 12 (2): 309–13. doi:10.3892/ijo.12.2.309. PMID9458354.
Lin L, Xu B, Rote NS (January 2000). "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. doi:10.1053/plac.1999.0443. PMID10692254.
Kim H, Crow TJ, Hyun BH (2000). "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. doi:10.1159/000015579. PMID10894926. S2CID85042388.