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Gene Review

env  -  gp160; envelope glycoprotein

Human immunodeficiency virus 1

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Disease relevance of env


Psychiatry related information on env


High impact information on env

  • The beta-chemokine receptors CKR-3 and CKR-2b support HIV-1 89.6 env-mediated syncytia formation but do not support fusion by any of the T-tropic or M-tropic strains tested [8].
  • Escape virus contained mutations in the env gene that were unexpectedly sparse, did not map generally to known neutralization epitopes, and involved primarily changes in N-linked glycosylation [9].
  • In this report we analyze the immunogenicity and efficacy of an HIV-1 DNA vaccine encoding env, rev and gag/pol in a chimpanzee model system [10].
  • This variant, designated X10-1, was derived from the genome of a cytopathic HTLV-III clone (pHXB2D) by excision of a 200-base pair segment in the 3' region of the virus, spanning the env and 3'-orf genes [11].
  • It is proposed that this second messenger RNA is the transcript of a gene (3'-orf) located after the env gene [12].

Chemical compound and disease context of env

  • Nucleotide changes in env altered 12 amino acids in the gp120 and gp41 exterior domains, and a 140-bp deletion in env resulted in the substitution of the carboxyl terminus of the SIVmac gp41 glycoprotein for that of the HIV-1 gp41 glycoprotein [13].
  • When cells were treated with the CRM1 inhibitor leptomycin B in the presence of Rev protein, the env intron containing HIV RNAs formed clusters throughout the nucleoplasm and accumulated at the nuclear pores [14].
  • HIV-IT(V) is a retroviral vector encoding the HIV-1 IIIB env and rev genes and a neomycin resistance marker gene (neor) [15].
  • To test this hypothesis, we produced pseudotyped wild-type and vif-deleted HIV gpt virions (which contain the HIV-1 genome with the bacterial mycophenolic acid resistance gene gpt in place of the viral env gene) in permissive cells, and we used them to generate nonpermissive H9 leukemic T cells that express these proviruses [16].
  • In the case of the tetracycline-regulated system, cell lines (both HeLa and U937) were generated that displayed tight regulation of Rev. In the case of the HeLa cell lines, they were used for the subsequent generation of stable cell lines expressing either HIV-1 env or chloramphenicol acetyl transferase (CAT) in a Rev-dependent fashion [17].

Biological context of env

  • Genomic RNA and DNA from productively infected H9 cells were independently extracted and amplified in reactions with and without reverse transcriptase respectively using primer pairs to the gag, env, tat and nef regions of the viral genome in the same reaction mixture [18].
  • Nucleotide changes potentially responsible for the increased virulence of SHIV-89.6P were limited to the env, tat, or long terminal repeat sequences, with most of the observed changes in env [13].
  • Most detailed analyses of the human immunodeficiency virus type 1 (HIV-1) rev gene product have relied on transfection of subgenomic env constructs into cells in which amplification of the transfected DNA occurs [19].
  • A chimeric virus, SHIVKU-1bMC17, constructed with the consensus env from the SHIVKU-1b on a background of SHIV-4, confirmed that amino acid substitutions in Env were responsible for the neutralization-resistant phenotype [20].
  • These results suggest that the HIV-1-SIVmac chimeric virus will be useful for investigating genetic variation of HIV-1 env and alteration of biological properties in vivo in relation to the host immune response [21].

Anatomical context of env


Associations of env with chemical compounds

  • Thus selection for viral variants with full-length env-TM demonstrated that the cytoplasmic domain of the SIVmac env glycoprotein plays a role in viral persistence and immunodeficiency in primates [27].
  • To accomplish this, the env gene of an SIV vector was made defective by the insertion of a SV40 promoter/enhancer hygromycin B phosphotransferase gene cassette [28].
  • Moreover, in env clones with a high G to A transition rate, multiple in-frame stop codons were generated exclusively at tryptophan codons [29].
  • R5-AIDS env pseudotypes were more resistant to TAK-779 and showed more rapid infection kinetics but similar resistance to a CD4 blocking mAb [30].
  • Analyses of the recombination breakpoints and mechanistic studies revealed that the presence of a recombination hotspot in the C3/V4 env region, unique to 115-A as donor RNA, could account for the higher recombination frequencies with the 115-A virus/template [31].

Physical interactions of env

  • Here we show that this Rev response requires a specific target sequence which coincides with a complex RNA secondary structure present in the env gene [32].

Regulatory relationships of env

  • In the nuclear expression system, Rev enhanced env mRNA transport by about 1.6-fold, while translation of this mRNA was increased more than a 100-fold [33].
  • ENF resistance mutations, selected in vitro or in vivo, were introduced into the env gene of HIV-1(NL4-3) by site-directed mutagenesis and expressed in HIV-1 recombinants carrying sequence tags in nef [34].

Other interactions of env

  • A simian human immunodeficiency virus with a nonfunctional Vpu (deltavpuSHIV(KU-1bMC33)) isolated from a macaque with neuroAIDS has selected for mutations in env and nef that contributed to its pathogenic phenotype [24].
  • The data presented herein show that the HIV-1 primed CD4(+) T cells produced the R5 suppression factor in response to a wide variety of HIV-1 gag, env, pol, nef or vif peptides, depending on the donor of the CD4(+) T cells [35].
  • The HIV-1 Rev protein facilitates the cytoplasmic accumulation of the intron-containing viral gag-pol and env mRNAs and is required for viral replication [36].
  • Our results suggest that productive infection of primary macrophages with T-cell-tropic strains of HIV-1 is determined by two different genetic mechanisms: one effective at the virus/cell entry, controlled by the env gene, and the second after entry, controlled by genes vif and vpr [37].

Analytical, diagnostic and therapeutic context of env

  • HIV-1 subtyping using gag/env heteroduplex mobility assay and peptide enzyme-linked immunosorbent assay [38].
  • HIV-1 PCR with env, nef, and vif gene primers was done on 43 persistently seronegative prostitutes who remained seronegative after 3 or more years of follow-up [39].
  • Northern blots (using an env probe) demonstrated the existence of all major HIV RNA species (9.3-, 4.3-, and 2.0-kb mRNA) in HIV-infected cells treated with antisense env RNA although at a reduced level [40].
  • SIV/HIV-1 chimeric viruses having HIV-1 env gene: a new animal model and a candidate for attenuated live vaccine [41].
  • To determine the specificity of circulating HIV-immune CTL in humans, a panel of doubly transfected mouse P815 tumor cells was produced which express the human HLA-A2 or HLA-A3 transplantation antigen gene and one HIV-1 gene (env, gag or nef) [42].


  1. Rev is necessary for translation but not cytoplasmic accumulation of HIV-1 vif, vpr, and env/vpu 2 RNAs. Arrigo, S.J., Chen, I.S. Genes Dev. (1991) [Pubmed]
  2. Structure-function analyses of the HTLV-I Rex and HIV-1 Rev RNA response elements: insights into the mechanism of Rex and Rev action. Ahmed, Y.F., Hanly, S.M., Malim, M.H., Cullen, B.R., Greene, W.C. Genes Dev. (1990) [Pubmed]
  3. Human immunodeficiency virus type 1 has an additional coding sequence in the central region of the genome. Matsuda, Z., Chou, M.J., Matsuda, M., Huang, J.H., Chen, Y.M., Redfield, R., Mayer, K., Essex, M., Lee, T.H. Proc. Natl. Acad. Sci. U.S.A. (1988) [Pubmed]
  4. Targeting of the human immunodeficiency virus type 1 envelope to the trans-Golgi network through binding to TIP47 is required for env incorporation into virions and infectivity. Blot, G., Janvier, K., Le Panse, S., Benarous, R., Berlioz-Torrent, C. J. Virol. (2003) [Pubmed]
  5. The origin of human immunodeficiency virus type-1 rev gene. An evolutionary hypothesis. Kubota, S., Oroszlan, S., Hatanaka, M. FEBS Lett. (1994) [Pubmed]
  6. Increased human immunodeficiency virus type 1 (HIV-1) env compartmentalization in the presence of HIV-1-associated dementia. Ritola, K., Robertson, K., Fiscus, S.A., Hall, C., Swanstrom, R. J. Virol. (2005) [Pubmed]
  7. Genotypic and phenotypic correlates of the HIV Type 1 env gene evolution in infected children with discordant response to antiretroviral therapy. Bagnarelli, P., Vecchi, M., Burighel, N., Bellanova, D., Menzo, S., Clementi, M., De Rossi, A. AIDS Res. Hum. Retroviruses (2004) [Pubmed]
  8. 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]
  9. Antibody neutralization and escape by HIV-1. Wei, X., Decker, J.M., Wang, S., Hui, H., Kappes, J.C., Wu, X., Salazar-Gonzalez, J.F., Salazar, M.G., Kilby, J.M., Saag, M.S., Komarova, N.L., Nowak, M.A., Hahn, B.H., Kwong, P.D., Shaw, G.M. Nature (2003) [Pubmed]
  10. Protection of chimpanzees from high-dose heterologous HIV-1 challenge by DNA vaccination. Boyer, J.D., Ugen, K.E., Wang, B., Agadjanyan, M., Gilbert, L., Bagarazzi, M.L., Chattergoon, M., Frost, P., Javadian, A., Williams, W.V., Refaeli, Y., Ciccarelli, R.B., McCallus, D., Coney, L., Weiner, D.B. Nat. Med. (1997) [Pubmed]
  11. Infectious mutants of HTLV-III with changes in the 3' region and markedly reduced cytopathic effects. Fisher, A.G., Ratner, L., Mitsuya, H., Marselle, L.M., Harper, M.E., Broder, S., Gallo, R.C., Wong-Staal, F. Science (1986) [Pubmed]
  12. Trans-activator gene of human T-lymphotropic virus type III (HTLV-III). Arya, S.K., Guo, C., Josephs, S.F., Wong-Staal, F. Science (1985) [Pubmed]
  13. Characterization of molecularly cloned simian-human immunodeficiency viruses causing rapid CD4+ lymphocyte depletion in rhesus monkeys. Karlsson, G.B., Halloran, M., Li, J., Park, I.W., Gomila, R., Reimann, K.A., Axthelm, M.K., Iliff, S.A., Letvin, N.L., Sodroski, J. J. Virol. (1997) [Pubmed]
  14. Rev inhibition strongly affects intracellular distribution of human immunodeficiency virus type 1 RNAs. Cmarko, D., Bøe, S.O., Scassellati, C., Szilvay, A.M., Davanger, S., Fu, X.D., Haukenes, G., Kalland, K.H., Fakan, S. J. Virol. (2002) [Pubmed]
  15. Evidence for localization of biologically active recombinant retroviral vector to lymph nodes in mice injected intramuscularly. Kamantigue, E., Edwards, W., Chada, S., Brumm, D., Austin, M., Irwin, M., Mento, S., Kowal, K., Sajjadi, N. Gene Ther. (1996) [Pubmed]
  16. An endogenous inhibitor of human immunodeficiency virus in human lymphocytes is overcome by the viral Vif protein. Madani, N., Kabat, D. J. Virol. (1998) [Pubmed]
  17. Regulated expression of HIV-1 Rev function in mammalian cell lines. Swenarchuk, L., Harakidas, P., Cochrane, A. Can. J. Microbiol. (1999) [Pubmed]
  18. Co-amplification of multiple regions of the HIV-1 genome by the polymerase chain reaction: potential use in multiple diagnosis. Hewlett, I.K., Ruta, M., Cristiano, K., Hawthorne, C.A., Epstein, J.S. Oncogene (1989) [Pubmed]
  19. Analysis of rev gene function on human immunodeficiency virus type 1 replication in lymphoid cells by using a quantitative polymerase chain reaction method. Arrigo, S.J., Weitsman, S., Rosenblatt, J.D., Chen, I.S. J. Virol. (1989) [Pubmed]
  20. Characterization of a neutralization-escape variant of SHIVKU-1, a virus that causes acquired immune deficiency syndrome in pig-tailed macaques. Narayan, S.V., Mukherjee, S., Jia, F., Li, Z., Wang, C., Foresman, L., McCormick-Davis, C., Stephens, E.B., Joag, S.V., Narayan, O. Virology (1999) [Pubmed]
  21. Genomic and biological alteration of a human immunodeficiency virus type 1 (HIV-1)-simian immunodeficiency virus strain mac chimera, with HIV-1 Env, recovered from a long-term carrier monkey. Igarashi, T., Kuwata, T., Takehisa, J., Ibuki, K., Shibata, R., Mukai, R., Komatsu, T., Adachi, A., Ido, E., Hayami, M. J. Gen. Virol. (1996) [Pubmed]
  22. Dendritic cells transduced by multiply deleted HIV-1 vectors exhibit normal phenotypes and functions and elicit an HIV-specific cytotoxic T-lymphocyte response in vitro. Gruber, A., Kan-Mitchell, J., Kuhen, K.L., Mukai, T., Wong-Staal, F. Blood (2000) [Pubmed]
  23. Mechanism of translation of monocistronic and multicistronic human immunodeficiency virus type 1 mRNAs. Schwartz, S., Felber, B.K., Pavlakis, G.N. Mol. Cell. Biol. (1992) [Pubmed]
  24. A simian human immunodeficiency virus with a nonfunctional Vpu (deltavpuSHIV(KU-1bMC33)) isolated from a macaque with neuroAIDS has selected for mutations in env and nef that contributed to its pathogenic phenotype. Singh, D.K., McCormick, C., Pacyniak, E., Lawrence, K., Dalton, S.B., Pinson, D.M., Sun, F., Berman, N.E., Calvert, M., Gunderson, R.S., Wong, S.W., Stephens, E.B. Virology (2001) [Pubmed]
  25. Infected macaques that controlled replication of SIVmac or nonpathogenic SHIV developed sterilizing resistance against pathogenic SHIV(KU-1). Stephens, E.B., Joag, S.V., Atkinson, B., Sahni, M., Li, Z., Foresman, L., Adany, I., Narayan, O. Virology (1997) [Pubmed]
  26. Intracellular membrane traffic of human immunodeficiency virus type 1 envelope glycoproteins: vpu liberates Golgi-targeted gp160 from CD4-dependent retention in the endoplasmic reticulum. Kimura, T., Nishikawa, M., Ohyama, A. J. Biochem. (1994) [Pubmed]
  27. Importance of the intracytoplasmic domain of the simian immunodeficiency virus (SIV) envelope glycoprotein for pathogenesis. Luciw, P.A., Shaw, K.E., Shacklett, B.L., Marthas, M.L. Virology (1998) [Pubmed]
  28. Rev/RRE-independent Mason-Pfizer monkey virus constitutive transport element-dependent propagation of SIVmac239 vectors using a single round of replication assay. Rizvi, T.A., Schmidt, R.D., Lew, K.A., Keeling, M.E. Virology (1996) [Pubmed]
  29. The genetic fate of molecularly cloned simian immunodeficiency virus in experimentally infected macaques. Johnson, P.R., Hamm, T.E., Goldstein, S., Kitov, S., Hirsch, V.M. Virology (1991) [Pubmed]
  30. The envelope gene is a cytopathic determinant of CCR5 tropic HIV-1. Olivieri, K., Scoggins, R.M., Bor, Y.C., Matthews, A., Mark, D., Taylor, J.R., Chernauskas, D., Hammarskj??ld, M.L., Rekosh, D., Camerini, D. Virology (2007) [Pubmed]
  31. Influence of sequence identity and unique breakpoints on the frequency of intersubtype HIV-1 recombination. Baird, H.A., Gao, Y., Galetto, R., Lalonde, M., Anthony, R.M., Giacomoni, V., Abreha, M., Destefano, J.J., Negroni, M., Arts, E.J. Retrovirology (2006) [Pubmed]
  32. The HIV-1 rev trans-activator acts through a structured target sequence to activate nuclear export of unspliced viral mRNA. Malim, M.H., Hauber, J., Le, S.Y., Maizel, J.V., Cullen, B.R. Nature (1989) [Pubmed]
  33. Regulation of HIV-1 env mRNA translation by Rev protein. Perales, C., Carrasco, L., González, M.E. Biochim. Biophys. Acta (2005) [Pubmed]
  34. Relative replicative fitness of human immunodeficiency virus type 1 mutants resistant to enfuvirtide (T-20). Lu, J., Sista, P., Giguel, F., Greenberg, M., Kuritzkes, D.R. J. Virol. (2004) [Pubmed]
  35. Identification of HIV-1 epitopes that induce the synthesis of a R5 HIV-1 suppression factor by human CD4+ T cells isolated from HIV-1 immunized hu-PBL SCID mice. Yoshida, A., Tanaka, R., Kodama, A., Yamamoto, N., Ansari, A.A., Tanaka, Y. Clin. Dev. Immunol. (2005) [Pubmed]
  36. The cellular HIV-1 Rev cofactor hRIP is required for viral replication. Yu, Z., Sánchez-Velar, N., Catrina, I.E., Kittler, E.L., Udofia, E.B., Zapp, M.L. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  37. Genetic control of infection of primary macrophages with T-cell-tropic strains of HIV-1. Hirsch, I., de Mareuil, J., Salaun, D., Chermann, J.C. Virology (1996) [Pubmed]
  38. HIV-1 subtyping using gag/env heteroduplex mobility assay and peptide enzyme-linked immunosorbent assay. Simparak, W., Kositanont, U., Sutthent, R., Wasinrapee, P., Chaowanachan, T., Wasi, C. Asian Pac. J. Allergy Immunol. (2005) [Pubmed]
  39. Resistance to HIV-1 infection among persistently seronegative prostitutes in Nairobi, Kenya. Fowke, K.R., Nagelkerke, N.J., Kimani, J., Simonsen, J.N., Anzala, A.O., Bwayo, J.J., MacDonald, K.S., Ngugi, E.N., Plummer, F.A. Lancet (1996) [Pubmed]
  40. Inhibition of expression of human immunodeficiency virus-1 in vitro by antibody-targeted liposomes containing antisense RNA to the env region. Renneisen, K., Leserman, L., Matthes, E., Schröder, H.C., Müller, W.E. J. Biol. Chem. (1990) [Pubmed]
  41. SIV/HIV-1 chimeric viruses having HIV-1 env gene: a new animal model and a candidate for attenuated live vaccine. Hayami, M., Igarashi, T. Leukemia (1997) [Pubmed]
  42. Multiple subsets of HIV-specific cytotoxic T lymphocytes in humans and in mice. Chenciner, N., Michel, F., Dadaglio, G., Langlade-Demoyen, P., Hoffenbach, A., Leroux, A., Garcia-Pons, F., Rautmann, G., Guy, B., Guillon, J.M. Eur. J. Immunol. (1989) [Pubmed]
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