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Gene Review

ERVW-1  -  endogenous retrovirus group W, member 1

Homo sapiens

Synonyms: ENV, ENVW, ERVWE1, Endogenous retrovirus group W member 1, Env-W, ...
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Disease relevance of ERVWE1

  • Sequencing of the critical elements of the ERVWE1 provirus showed a striking conservation among the 48 alleles of 24 individuals, including the LTR elements involved in the transcriptional machinery, the splice sites involved in the maturation of subgenomic Env mRNA, and the Env ORF [1].
  • Fusion was observed for two human endogenous retrovirus (HERV) envelopes, the previously characterized HERV-W envelope, also called syncytin, and a previously uncharacterized gene from the HERV-FRD family [2].
  • The recognition of ASCT1 and ASCT2 despite this divergence of their sequences strongly suggests that the use of both receptors has been highly advantageous for survival and evolution of the HERV-W family of retroviruses [3].
  • HERV env proteins are frequently transcribed and translated in ovarian epithelial tumors, and multiple HERV families are detectable in ovarian cancer [4].
  • Human endogenous retrovirus type W (HERV-W) envelope glycoprotein (Env) has recently been reported to induce fusion in cells expressing the RD-114 and type D retrovirus receptor (RDR) and to serve as a functional retroviral envelope protein [5].

Psychiatry related information on ERVWE1

  • Similarly, elevated HERV-W levels were detected in patients with Alzheimer's dementia only when tumor necrosis factor-alpha expression was also evident (2 of 6 cases) [6].
  • HERV-W-related RNA detected in plasma from individuals with recent-onset schizophrenia or schizoaffective disorder [7].
  • As a model for Neuropsychiatric dysfunction in NeuroAIDS due to HIV-1 infection and drug abuse, we analyzed gene expression in human neurons treated with cocaine and HIV-1 proteins tat and envelope (env) [8].

High impact information on ERVWE1

  • Our results suggest that the T-tropic viruses characteristic of disease progression may evolve from purely M-tropic viruses prevalent early in virus infection through changes in the env protein that enable the virus to use multiple entry cofactors [9].
  • The smaller RNA does not contain gag-, pol- or env-specific nucleotide sequences but does carry nucleotide sequences from both the 5' and 3' termini of the genome, suggesting that it may be a subgenomic mRNA [10].
  • The 7.2 kb species, which is presumably the genome of AMV, appears to contain the entire retroviral gag gene and at least part of the pol gene, but lacks much (or all) of the env gene [10].
  • The genome of MSV was shown to retain approximately 0.13 kb from the 5' end of the MuLV env region, including sequences which span the point in the MuLV env mRNA [11].
  • Several strains of ASV were compared with respect to these sites, and the sites have been located in relation to deletions frequently observed in the env and src genes of ASV [12].

Chemical compound and disease context of ERVWE1


Biological context of ERVWE1


Anatomical context of ERVWE1

  • In addition, although HERV-W Env mediates only slight syncytium formation or infection of mouse cells, it utilizes the mouse transporters mASCT1 and mASCT2 when their sites for N-linked glycosylation are eliminated by mutagenesis [3].
  • The envelope glycoprotein (Env) encoded by HERV-W is highly fusogenic, is naturally expressed in human placental syncytiatrophoblasts, and has been reported to function as a superantigen in lymphocyte cultures [3].
  • Therefore, the relative levels of 3.1 kb and 8 kb mRNAs in trophoblasts could regulate syncytin protein synthesis, possibly by competition of the two mRNA species for translational apparatus [19].
  • An RT-PCR approach indicated that the env gene was expressed in several human tissues (brain, prostate, testis, kidney, placenta, thymus, and uterus) and cancer cells (RT4, BT-474, MCF7, OVCAR-3, LOX-IMVI, and AZ521) [20].
  • We show that expression of recombinant syncytin in a wide variety of cell types induces the formation of giant syncytia, and that fusion of a human trophoblastic cell line expressing endogenous syncytin can be inhibited by an anti-syncytin antiserum [21].

Associations of ERVWE1 with chemical compounds

  • Although hamster cells are fully resistant to these viruses and murine cells are susceptible only to BaEV and HERV-W pseudotype viruses, these rodent cells both become highly susceptible to all of the viruses after treatment with tunicamycin, an inhibitor of protein N-linked glycosylation [22].
  • Second, we observed that in vitro stimulation of trophoblast cell fusion and differentiation by cyclic AMP is also associated with a concomitant increase in HERV-W env and hCG mRNA and protein expression [23].
  • This effect appears specific for the Pr65gag polyprotein, since the env precursor polyprotein Pr80env was normally synthesized and remained undegraded in cerulenin-treated 3JE-infected cells [24].
  • Na(+)-dependent alpha-(methylamino)isobutyric acid insensitive L -alanine transport was similarly decreased significantly in cells treated with forskolin suggesting that there is modulation of cell surface expression of the syncytin receptor associated with syncytialization [25].
  • We report the results of an preliminary examination of the methylation status of CpG dinucleotides associated with the L1 and HERV-W retrotransposons in benign and malignant human ovarian tumors [26].

Physical interactions of ERVWE1


Regulatory relationships of ERVWE1


Other interactions of ERVWE1

  • A widely dispersed interference group of retroviruses that includes the feline endogenous virus (RD114), baboon endogenous virus (BaEV), human endogenous virus type W (HERV-W), and type D primate retroviruses uses the human Na(+)-dependent neutral amino acid transporter type 2 (hASCT2; gene name, SLC1A5) as a common cell surface receptor [22].
  • In addition, we investigated the env gene expression of HERV-R in various human tissues and cancer cells [20].
  • Here we have analyzed the temporal regulation of mRNA expression of these genes in placenta and demonstrate that Syncytin gene activation is highest in term placenta, PEG10, downregulated at early hypoxic phase, and highly activated at 11-12 wk of gestation [19].
  • The env expression was increased by ATRA in a dose-dependent manner, while the expression of transglutaminase 1 (TGM1), a terminal marker for squamous differentiation, was decreased [32].
  • The presence of HERV-W env sequences was confirmed in stably transfected cell clones by using polymerase chain reaction [5].

Analytical, diagnostic and therapeutic context of ERVWE1


  1. The endogenous retroviral locus ERVWE1 is a bona fide gene involved in hominoid placental physiology. Mallet, F., Bouton, O., Prudhomme, S., Cheynet, V., Oriol, G., Bonnaud, B., Lucotte, G., Duret, L., Mandrand, B. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  2. Genomewide screening for fusogenic human endogenous retrovirus envelopes identifies syncytin 2, a gene conserved on primate evolution. Blaise, S., de Parseval, N., Bénit, L., Heidmann, T. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  3. The envelope glycoprotein of human endogenous retrovirus type W uses a divergent family of amino acid transporters/cell surface receptors. Lavillette, D., Marin, M., Ruggieri, A., Mallet, F., Cosset, F.L., Kabat, D. J. Virol. (2002) [Pubmed]
  4. Expression of multiple human endogenous retrovirus surface envelope proteins in ovarian cancer. Wang-Johanning, F., Liu, J., Rycaj, K., Huang, M., Tsai, K., Rosen, D.G., Chen, D.T., Lu, D.W., Barnhart, K.F., Johanning, G.L. Int. J. Cancer (2007) [Pubmed]
  5. The envelope glycoprotein of human endogenous retrovirus HERV-W induces cellular resistance to spleen necrosis virus. Ponferrada, V.G., Mauck, B.S., Wooley, D.P. Arch. Virol. (2003) [Pubmed]
  6. Monocyte activation and differentiation augment human endogenous retrovirus expression: implications for inflammatory brain diseases. Johnston, J.B., Silva, C., Holden, J., Warren, K.G., Clark, A.W., Power, C. Ann. Neurol. (2001) [Pubmed]
  7. HERV-W-related RNA detected in plasma from individuals with recent-onset schizophrenia or schizoaffective disorder. Karlsson, H., Schröder, J., Bachmann, S., Bottmer, C., Yolken, R.H. Mol. Psychiatry (2004) [Pubmed]
  8. Gene chromosomal organization and expression in cultured human neurons exposed to cocaine and HIV-1 proteins gp120 and tat: drug abuse and NeuroAIDS. Shapshak, P., Duncan, R., Nath, A., Turchan, J., Pandjassarame, K., Rodriguez, H., Duran, E.M., Ziegler, F., Amaro, E., Lewis, A., Rodriguez, A., Minagar, A., Davis, W., Seth, R., Elkomy, F.F., Chiappelli, F., Kazic, T. Front. Biosci. (2006) [Pubmed]
  9. A dual-tropic primary HIV-1 isolate that uses fusin and the beta-chemokine receptors CKR-5, CKR-3, and CKR-2b as fusion cofactors. Doranz, B.J., Rucker, J., Yi, Y., Smyth, R.J., Samson, M., Peiper, S.C., Parmentier, M., Collman, R.G., Doms, R.W. Cell (1996) [Pubmed]
  10. The genome and the intracellular RNAs of avian myeloblastosis virus. Gonda, T.J., Sheiness, D.K., Fanshier, L., Bishop, J.M., Moscovici, C., Moscovici, M.G. Cell (1981) [Pubmed]
  11. An MSV-specific subgenomic mRNA in MSV-transformed G8-124 cells. Donoghue, D.J., Sharp, P.A., Weinberg, R.A. Cell (1979) [Pubmed]
  12. Mapping unintegrated avian sarcoma virus DNA: termini of linear DNA bear 300 nucleotides present once or twice in two species of circular DNA. Shank, P.R., Hughes, S.H., Kung, H.J., Majors, J.E., Quintrell, N., Guntaka, R.V., Bishop, J.M., Varmus, H.E. Cell (1978) [Pubmed]
  13. Human endogenous retrovirus glycoprotein-mediated induction of redox reactants causes oligodendrocyte death and demyelination. Antony, J.M., van Marle, G., Opii, W., Butterfield, D.A., Mallet, F., Yong, V.W., Wallace, J.L., Deacon, R.M., Warren, K., Power, C. Nat. Neurosci. (2004) [Pubmed]
  14. The molecular epidemiology and drug resistance determination of HIV type 1 subtype B infection in Barbados. Gittens, M.V., Roth, W.W., Roach, T., Stringer, H.G., Pieniazek, D., Bond, V.C., Levett, P.N. AIDS Res. Hum. Retroviruses (2003) [Pubmed]
  15. Transcriptional effects of hypoxia on fusiogenic syncytin and its receptor ASCT2 in human cytotrophoblast BeWo cells and in ex vivo perfused placental cotyledons. Knerr, I., Weigel, C., Linnemann, K., Dötsch, J., Meissner, U., Fusch, C., Rascher, W. Am. J. Obstet. Gynecol. (2003) [Pubmed]
  16. Assessment of HIV-1 subtyping for Cameroon strains using phylogenetic analysis of pol gene sequences. Njouom, R., Pasquier, C., Sandres-Sauné, K., Harter, A., Souyris, C., Izopet, J. J. Virol. Methods (2003) [Pubmed]
  17. Evidence of selection on the domesticated ERVWE1 env retroviral element involved in placentation. Bonnaud, B., Bouton, O., Oriol, G., Cheynet, V., Duret, L., Mallet, F. Mol. Biol. Evol. (2004) [Pubmed]
  18. A retroviral promoter and a cellular enhancer define a bipartite element which controls env ERVWE1 placental expression. Prudhomme, S., Oriol, G., Mallet, F. J. Virol. (2004) [Pubmed]
  19. Temporal regulation of the expression of syncytin (HERV-W), maternally imprinted PEG10, and SGCE in human placenta. Smallwood, A., Papageorghiou, A., Nicolaides, K., Alley, M.K., Jim, A., Nargund, G., Ojha, K., Campbell, S., Banerjee, S. Biol. Reprod. (2003) [Pubmed]
  20. Human Endogenous Retrovirus (HERV)-R family in primates: Chromosomal location, gene expression, and evolution. Kim, H.S., Yi, J.M., Hirai, H., Huh, J.W., Jeong, M.S., Jang, S.B., Kim, C.G., Saitou, N., Hyun, B.H., Lee, W.H. Gene (2006) [Pubmed]
  21. Syncytin is a captive retroviral envelope protein involved in human placental morphogenesis. Mi, S., Lee, X., Li, X., Veldman, G.M., Finnerty, H., Racie, L., LaVallie, E., Tang, X.Y., Edouard, P., Howes, S., Keith, J.C., McCoy, J.M. Nature (2000) [Pubmed]
  22. N-linked glycosylation and sequence changes in a critical negative control region of the ASCT1 and ASCT2 neutral amino acid transporters determine their retroviral receptor functions. Marin, M., Lavillette, D., Kelly, S.M., Kabat, D. J. Virol. (2003) [Pubmed]
  23. Direct involvement of HERV-W Env glycoprotein in human trophoblast cell fusion and differentiation. Frendo, J.L., Olivier, D., Cheynet, V., Blond, J.L., Bouton, O., Vidaud, M., Rabreau, M., Evain-Brion, D., Mallet, F. Mol. Cell. Biol. (2003) [Pubmed]
  24. The effect of cerulenin on the synthesis of the precursor gag polyprotein in defective murine leukemia and sarcoma virus producing cell lines. Ikuta, K., Coward, J., Luftig, R.B. Virology (1986) [Pubmed]
  25. Changes in expression and function of syncytin and its receptor, amino acid transport system B(0) (ASCT2), in human placental choriocarcinoma BeWo cells during syncytialization. Kudo, Y., Boyd, C.A. Placenta (2002) [Pubmed]
  26. L1 and HERV-W retrotransposons are hypomethylated in human ovarian carcinomas. Menendez, L., Benigno, B.B., McDonald, J.F. Mol. Cancer (2004) [Pubmed]
  27. Identification of the hASCT2-binding domain of the Env ERVWE1/syncytin-1 fusogenic glycoprotein. Cheynet, V., Oriol, G., Mallet, F. Retrovirology (2006) [Pubmed]
  28. Expression of human endogenous retrovirus type K envelope glycoprotein in insect and mammalian cells. Tönjes, R.R., Limbach, C., Löwer, R., Kurth, R. J. Virol. (1997) [Pubmed]
  29. Functional characterization of the placental fusogenic membrane protein syncytin. Chang, C., Chen, P.T., Chang, G.D., Huang, C.J., Chen, H. Biol. Reprod. (2004) [Pubmed]
  30. HERV-K: the biologically most active human endogenous retrovirus family. Tönjes, R.R., Löwer, R., Boller, K., Denner, J., Hasenmaier, B., Kirsch, H., König, H., Korbmacher, C., Limbach, C., Lugert, R., Phelps, R.C., Scherer, J., Thelen, K., Löwer, J., Kurth, R. J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. (1996) [Pubmed]
  31. Proliferation and cell-cell fusion of endometrial carcinoma are induced by the human endogenous retroviral Syncytin-1 and regulated by TGF-beta. Strick, R., Ackermann, S., Langbein, M., Swiatek, J., Schubert, S.W., Hashemolhosseini, S., Koscheck, T., Fasching, P.A., Schild, R.L., Beckmann, M.W., Strissel, P.L. J. Mol. Med. (2007) [Pubmed]
  32. Short communication: expression of human endogenous retrovirus-R gene links to differentiation of squamous cells. Otsuka, N., Miyatake, Y., Ishizu, A., Tanaka, S., Yamamoto, Y., Ikeda, H., Yoshiki, T. AIDS Res. Hum. Retroviruses (2006) [Pubmed]
  33. Expression of human endogenous retrovirus k envelope transcripts in human breast cancer. Wang-Johanning, F., Frost, A.R., Johanning, G.L., Khazaeli, M.B., LoBuglio, A.F., Shaw, D.R., Strong, T.V. Clin. Cancer Res. (2001) [Pubmed]
  34. ERV3 and related sequences in humans: structure and RNA expression. Andersson, A.C., Yun, Z., Sperber, G.O., Larsson, E., Blomberg, J. J. Virol. (2005) [Pubmed]
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