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Gene Review

env  -  envelope protein

Simian immunodeficiency virus

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Disease relevance of env

  • The dynamics of plasma viremia were explored in a group of 12 simian immunodeficiency virus (SIV)-infected rhesus macaques (Macaca mulatta) that had received prior immunization with either nonrecombinant or trivalent (gag-pol, env) SIV-recombinant vaccinia viruses [1].
  • Cynomolgus macaques were immunized intramuscularly with modified vaccinia virus Ankara (MVA) expressing the SIVsm env and gag-pol genes (MVA-SIVsm) at 0 and 3 months (n=4), at 0, 3 and 8 months (n=4) or at 0 and 3 months followed by purified native SIVsm gp148 and recombinant SIVmac p27 in immunostimulatory complexes at 8 months (n=4) [2].
  • Targeting a type I transmembrane protein, the HIV-1 envelope (env) protein, for expression in the cytoplasm, rather than allowing its normal co-translational translocation into the endoplasmic reticulum, sensitized target cells expressing this mutant more rapidly for lysis by an env-specific CTL clone [3].
  • In this study, the ability of a recombinant canarypox virus expressing SIV Gag-Pol-Env (ALVAC/SIV gag-pol-env) was assessed for its ability to elicit both dominant and subdominant epitope-specific CTL responses in rhesus monkeys [4].
  • A highly pathogenic simian/human immunodeficiency virus (SHIV), designated C2/1, was obtained by serum passages in cynomolgus monkeys of p-SHIV, an SHIV strain that contains the env gene of pathogenic human immunodeficiency virus type 1 89 [5].

Psychiatry related information on env


High impact information on env


Chemical compound and disease context of env


Biological context of env

  • Nucleotide sequence and phylogenetic analyses of the C2 to V5 region of env (C2-V5env) in proviral DNA from peripheral blood lymphocytes obtained 22 months before death revealed two distinct virus populations [15].
  • Heteroduplex mobility assay and partial sequence analysis of env and gag genes strongly suggests that all the HIV-infected subjects were infected with clade C HIV-1 [16].
  • Proviral clone pSIV BA was constructed by introducing a premature termination codon at codon 40 of the nef gene without altering the predicted amino acid sequence of the overlapping env gene [17].
  • In pHP, the long terminal repeats (LTRs), the 5' untranslated leader and portions of the env and nef genes were deleted [18].
  • Helper virus-free vector transfer was consistently achieved when the helper virus gag-pol and env genes were expressed from separate plasmids such that two recombination events were required to form an infectious genome [19].

Anatomical context of env

  • Analysis of additional recombinants revealed that syncytium formation, but not virus production, was controlled by a 1.4-kb viral DNA fragment in SIVmac-1A11 encoding only the external env glycoprotein gp130 [20].
  • We have examined the effect of a nef deletion on the infection of primary human CD4+ T lymphocytes and macrophages, using clones with nef and env sequences derived, respectively, from T cell- and macrophage-tropic viruses [21].
  • In both cases we observed that viral expression was mostly limited to early regulatory genes after a transient phase of late viral gene expression (i.e. env and gag), as reported for HIV-1-infected astrocytes in vivo [22].
  • Our data demonstrate that the SIV Env gene products are expressed in cultured cells after infection with a recombinant Ad containing both SIV env and rev genes [23].
  • Rev is an essential HIV-1 regulatory protein that binds the Rev responsive element (RRE) within the env gene of the HIV-1 RNA genome and is involved in transport of unspliced or partially spliced viral mRNA from the cell nucleus to the cytoplasm [24].

Associations of env with chemical compounds

  • Viral replication was mapped by in situ hybridization for SIV env, gag, and nef RNA, and catecholaminergic varicosities from the ANS were mapped by sucrose phosphate glyoxylic acid chemofluorescence [25].
  • To determine the effect of the two distinct patterns of disease in the evolution of SIV/17E-Fr envelope, we analyzed env sequences from three morphine-dependent macaques that developed accelerated AIDS and three morphine-dependent macaques that developed AIDS at a slower rate and compared them to control macaques [11].
  • Site-directed mutagenesis of the env gene in this region showed that the arginine substitutions at positions 334 and/or 340 within the "V3" domain were fundamental to virus neutralization but other substitutions in the V2-V4 region added to the ease of its neutralization since it became neutralizable with much higher dilutions of serum [26].
  • After sequencing different regions of the env gene including V1-V2, V3, and the fusion domain of both viruses, we have found only an asparagine (N)-to-isoleucine (I) change in position 7 of the V3 loop [27].
  • Vaccination of cynomolgus macaques with beta-propiolactone inactivated SIVmacBK28 in Freund's adjuvant induced low but detectable levels of anti-SIV envelope (env) antibodies and T-cell responses and protected against challenge with the 32H isolate of SIVmac251 grown in C8166 cells [28].

Analytical, diagnostic and therapeutic context of env

  • Sequence analysis revealed a remarkably high level of similarity between their env and nef genes as well as their 3' LTR [29].
  • METHODS: Proviral DNA from longitudinally collected uncultured PBMC were subjected to PCR amplification in the nef gene and env V2 and V3 regions, followed by cloning, sequencing and phylogenetic analysis to establish evolutionary relationships between HIV-1 strains over time [30].
  • Intramuscular injection of an unadjuvanted HIV-1 envelope (env) DNA vaccine recruited few DCs to the injection site and elicited low-frequency, env-specific immune responses in mice [31].
  • Determination of the mass of individual molecules by scanning transmission electron microscopy confirmed that SIV virion-associated env and gp140 formed largely homogeneous populations of trimers [9].
  • Virion-associated env, obtained by crosslinking and detergent extraction, and non-crosslinked secreted env ectodomain (recombinant gp140) were purified by lentil-lectin chromatography and gel filtration as single predominant species [9].


  1. Patterns of viral replication correlate with outcome in simian immunodeficiency virus (SIV)-infected macaques: effect of prior immunization with a trivalent SIV vaccine in modified vaccinia virus Ankara. Hirsch, V.M., Fuerst, T.R., Sutter, G., Carroll, M.W., Yang, L.C., Goldstein, S., Piatak, M., Elkins, W.R., Alvord, W.G., Montefiori, D.C., Moss, B., Lifson, J.D. J. Virol. (1996) [Pubmed]
  2. Immunization with recombinant modified vaccinia virus Ankara can modify mucosal simian immunodeficiency virus infection and delay disease progression in macaques. Nilsson, C., Sutter, G., Walther-Jallow, L., ten Haaft, P., Akerblom, L., Heeney, J., Erfle, V., Böttiger, P., Biberfeld, G., Thorstensson, R. J. Gen. Virol. (2002) [Pubmed]
  3. Targeting of HIV-1 antigens for rapid intracellular degradation enhances cytotoxic T lymphocyte (CTL) recognition and the induction of de novo CTL responses in vivo after immunization. Tobery, T.W., Siliciano, R.F. J. Exp. Med. (1997) [Pubmed]
  4. Recombinant canarypox vaccine-elicited CTL specific for dominant and subdominant simian immunodeficiency virus epitopes in rhesus monkeys. Santra, S., Schmitz, J.E., Kuroda, M.J., Lifton, M.A., Nickerson, C.E., Lord, C.I., Pal, R., Franchini, G., Letvin, N.L. J. Immunol. (2002) [Pubmed]
  5. A highly pathogenic simian/human immunodeficiency virus with genetic changes in cynomolgus monkey. Shinohara, K., Sakai, K., Ando, S., Ami, Y., Yoshino, N., Takahashi, E., Someya, K., Suzaki, Y., Nakasone, T., Sasaki, Y., Kaizu, M., Lu, Y., Honda, M. J. Gen. Virol. (1999) [Pubmed]
  6. Lack of correlation between SIV-Nef evolution and rapid disease progression in morphine-dependent nonhuman primate model of AIDS. Noel, R.J., Toro-Bahamonde, A., Marrero-Otero, Z., Orsini, S., Verma, A.S., Kumar, R., Kumar, A. AIDS Res. Hum. Retroviruses (2006) [Pubmed]
  7. Generation of HIV-1 derivatives that productively infect macaque monkey lymphoid cells. Kamada, K., Igarashi, T., Martin, M.A., Khamsri, B., Hatcho, K., Yamashita, T., Fujita, M., Uchiyama, T., Adachi, A. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  8. Electron tomography analysis of envelope glycoprotein trimers on HIV and simian immunodeficiency virus virions. Zhu, P., Chertova, E., Bess, J., Lifson, J.D., Arthur, L.O., Liu, J., Taylor, K.A., Roux, K.H. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  9. Oligomeric structure of virion-associated and soluble forms of the simian immunodeficiency virus envelope protein in the prefusion activated conformation. Center, R.J., Schuck, P., Leapman, R.D., Arthur, L.O., Earl, P.L., Moss, B., Lebowitz, J. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  10. A Conserved Dileucine Motif Mediates Clathrin and AP-2-dependent Endocytosis of the HIV-1 Envelope Protein. Byland, R., Vance, P.J., Hoxie, J.A., Marsh, M. Mol. Biol. Cell (2007) [Pubmed]
  11. Variable region 4 of SIV envelope correlates with rapid disease progression in morphine-exposed macaques infected with SIV/SHIV. Rivera-Amill, V., Noel, R.J., Orsini, S., Tirado, G., García, J.M., Buch, S., Kumar, A. Virology (2007) [Pubmed]
  12. Oral DNA vaccination promotes mucosal and systemic immune responses to HIV envelope glycoprotein. Kaneko, H., Bednarek, I., Wierzbicki, A., Kiszka, I., Dmochowski, M., Wasik, T.J., Kaneko, Y., Kozbor, D. Virology (2000) [Pubmed]
  13. Preparative separation of foreign antigens for highly efficient presentation to T cells in vitro. Katrak, K., Mahon, B.P., Jones, W.C., Bräutigam, S., Mills, K.H. J. Immunol. Methods (1992) [Pubmed]
  14. High Incidence of Unusual Cysteine Variants in gp120 Envelope Proteins from Early HIV Type 1 Infections from a Phase 3 Vaccine Efficacy Trial. Jobes, D.V., Daoust, M., Nguyen, V., Padua, A., Michele, S., Lock, M.D., Chen, A., Sinangil, F., Berman, P.W. AIDS Res. Hum. Retroviruses (2006) [Pubmed]
  15. Extensive diversification of human immunodeficiency virus type 1 subtype B strains during dual infection of a chimpanzee that progressed to AIDS. Wei, Q., Fultz, P.N. J. Virol. (1998) [Pubmed]
  16. Cross-clade human immunodeficiency virus (HIV)-specific cytotoxic T-lymphocyte responses in HIV-infected Zambians. Betts, M.R., Krowka, J., Santamaria, C., Balsamo, K., Gao, F., Mulundu, G., Luo, C., N'Gandu, N., Sheppard, H., Hahn, B.H., Allen, S., Frelinger, J.A. J. Virol. (1997) [Pubmed]
  17. Simian immunodeficiency virus negative factor suppresses the level of viral mRNA in COS cells. Niederman, T.M., Hu, W., Ratner, L. J. Virol. (1991) [Pubmed]
  18. Efficacy and safety analyses of a recombinant human immunodeficiency virus type 1 derived vector system. Chang, L.J., Urlacher, V., Iwakuma, T., Cui, Y., Zucali, J. Gene Ther. (1999) [Pubmed]
  19. Helper virus-free transfer of human immunodeficiency virus type 1 vectors. Richardson, J.H., Kaye, J.F., Child, L.A., Lever, A.M. J. Gen. Virol. (1995) [Pubmed]
  20. Identification of viral determinants of macrophage tropism for simian immunodeficiency virus SIVmac. Banapour, B., Marthas, M.L., Ramos, R.A., Lohman, B.L., Unger, R.E., Gardner, M.B., Pedersen, N.C., Luciw, P.A. J. Virol. (1991) [Pubmed]
  21. The nef gene controls syncytium formation in primary human lymphocytes and macrophages infected by HIV type 1. Meylan, P.R., Baumgartner, M., Ciuffi, A., Munoz, M., Sahli, R. AIDS Res. Hum. Retroviruses (1998) [Pubmed]
  22. Simian immunodeficiency virus mac251 infection of astrocytes. Guillemin, G., Croitoru, J., Le Grand, R.L., Franck-Duchenne, M., Dormont, D., Boussin, F.D. J. Neurovirol. (2000) [Pubmed]
  23. Coexpression of the simian immunodeficiency virus Env and Rev proteins by a recombinant human adenovirus host range mutant. Cheng, S.M., Lee, S.G., Ronchetti-Blume, M., Virk, K.P., Mizutani, S., Eichberg, J.W., Davis, A., Hung, P.P., Hirsch, V.M., Chanock, R.M. J. Virol. (1992) [Pubmed]
  24. Mechanism of neomycin and Rev peptide binding to the Rev responsive element of HIV-1 as determined by fluorescence and NMR spectroscopy. Lacourciere, K.A., Stivers, J.T., Marino, J.P. Biochemistry (2000) [Pubmed]
  25. Enhanced replication of simian immunodeficiency virus adjacent to catecholaminergic varicosities in primate lymph nodes. Sloan, E.K., Tarara, R.P., Capitanio, J.P., Cole, S.W. J. Virol. (2006) [Pubmed]
  26. Neutralization of SIVmac239/17E in lymphocyte cultures involves virus strain-specific linear and conformational epitopes encoded by different regions of the env gene including the "V3" domain. Wu, Z., Qian, G., Zhen, Q.L., Narayan, O., Stephens, E.B. Virology (1996) [Pubmed]
  27. Phenotypic switch in a Spanish HIV type 1 isolate on serial passage on MT-4 cells. Olivares, I., Shaw, G., Lopez-Galindez, C. AIDS Res. Hum. Retroviruses (1997) [Pubmed]
  28. Protection against SIV infection in macaques by immunization with inactivated virus from the BK28 molecular clone, but not with BK28-derived recombinant env and gag proteins. Mills, K.H., Page, M., Chan, W.L., Kitchin, P., Stott, E.J., Taffs, F., Jones, W., Rose, J., Ling, C., Silvera, P. J. Med. Primatol. (1992) [Pubmed]
  29. Development and characterization of positively selected brain-adapted SIV. Gaskill, P.J., Watry, D.D., Burdo, T.H., Fox, H.S. Virol. J. (2005) [Pubmed]
  30. HIV-1 strains from a cohort of American subjects reveal the presence of a V2 region extension unique to slow progressors and non-progressors. Wang, B., Spira, T.J., Owen, S., Lal, R.B., Saksena, N.K. AIDS (2000) [Pubmed]
  31. Recruitment and expansion of dendritic cells in vivo potentiate the immunogenicity of plasmid DNA vaccines. Sumida, S.M., McKay, P.F., Truitt, D.M., Kishko, M.G., Arthur, J.C., Seaman, M.S., Jackson, S.S., Gorgone, D.A., Lifton, M.A., Letvin, N.L., Barouch, D.H. J. Clin. Invest. (2004) [Pubmed]
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