PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of jvirolPermissionsJournals.ASM.orgJournalJV ArticleJournal InfoAuthorsReviewers
 
J Virol. 1994 June; 68(6): 3682–3692.
PMCID: PMC236873

The "V3" domain is a determinant of simian immunodeficiency virus cell tropism.

Abstract

Thirty-one different mutant forms of simian immunodeficiency virus (SIVmac) were created with changes in the region of env corresponding to the V3 domain of HIV-1. Sixteen of these mutants had one amino acid change, 12 had two changes, two had three changes, and one had four changes in the SIVmac "V3" loop. The ability of the mutant viruses to replicate in CEMx174 cells, rhesus monkey peripheral blood mononuclear cells, and rhesus monkey alveolar macrophages was investigated. Ten of the mutant viruses replicated with approximately wild-type kinetics in all three cell types. Of the 31 mutants, 22 were able to replicate in one or more of the cell types. Thus, this region of SIVmac gp120 is quite tolerant to change. Nine of the mutants replicated poorly or not at all in any of the cells tested. The lack of replication competence of some of the mutants was associated with inefficient proteolytic processing of the gp160 precursor. Some mutations had dramatic differential effects in different cell types. For example, changing P to S at position 321 and M to I at position 325 drastically reduced replication in macrophages and CEMx174 cells but had no effect on replication in peripheral blood mononuclear cells. Mutants with altered tropism were blocked at an early stage that includes virus entry into cells. Thus, sequences in SIVmac that correspond to V3 in HIV-1 can affect virus entry and cell tropism in a manner analogous to that of HIV-1 V3.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (2.1M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Berger EA, Sisler JR, Earl PL. Human immunodeficiency virus type 1 envelope glycoprotein molecules containing membrane fusion-impairing mutations in the V3 region efficiently undergo soluble CD4-stimulated gp120 release. J Virol. 1992 Oct;66(10):6208–6212. [PMC free article] [PubMed]
  • Björling E, Broliden K, Bernardi D, Utter G, Thorstensson R, Chiodi F, Norrby E. Hyperimmune antisera against synthetic peptides representing the glycoprotein of human immunodeficiency virus type 2 can mediate neutralization and antibody-dependent cytotoxic activity. Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):6082–6086. [PubMed]
  • Boeri E, Giri A, Lillo F, Ferrari G, Varnier OE, Ferro A, Sabbatani S, Saxinger WC, Franchini G. In vivo genetic variability of the human immunodeficiency virus type 2 V3 region. J Virol. 1992 Jul;66(7):4546–4550. [PMC free article] [PubMed]
  • Burns DP, Desrosiers RC. Selection of genetic variants of simian immunodeficiency virus in persistently infected rhesus monkeys. J Virol. 1991 Apr;65(4):1843–1854. [PMC free article] [PubMed]
  • Cann AJ, Churcher MJ, Boyd M, O'Brien W, Zhao JQ, Zack J, Chen IS. The region of the envelope gene of human immunodeficiency virus type 1 responsible for determination of cell tropism. J Virol. 1992 Jan;66(1):305–309. [PMC free article] [PubMed]
  • Cheng-Mayer C, Quiroga M, Tung JW, Dina D, Levy JA. Viral determinants of human immunodeficiency virus type 1 T-cell or macrophage tropism, cytopathogenicity, and CD4 antigen modulation. J Virol. 1990 Sep;64(9):4390–4398. [PMC free article] [PubMed]
  • Chesebro B, Nishio J, Perryman S, Cann A, O'Brien W, Chen IS, Wehrly K. Identification of human immunodeficiency virus envelope gene sequences influencing viral entry into CD4-positive HeLa cells, T-leukemia cells, and macrophages. J Virol. 1991 Nov;65(11):5782–5789. [PMC free article] [PubMed]
  • Chesebro B, Wehrly K, Nishio J, Perryman S. Macrophage-tropic human immunodeficiency virus isolates from different patients exhibit unusual V3 envelope sequence homogeneity in comparison with T-cell-tropic isolates: definition of critical amino acids involved in cell tropism. J Virol. 1992 Nov;66(11):6547–6554. [PMC free article] [PubMed]
  • Clements GJ, Price-Jones MJ, Stephens PE, Sutton C, Schulz TF, Clapham PR, McKeating JA, McClure MO, Thomson S, Marsh M, et al. The V3 loops of the HIV-1 and HIV-2 surface glycoproteins contain proteolytic cleavage sites: a possible function in viral fusion? AIDS Res Hum Retroviruses. 1991 Jan;7(1):3–16. [PubMed]
  • Cordonnier A, Montagnier L, Emerman M. Single amino-acid changes in HIV envelope affect viral tropism and receptor binding. Nature. 1989 Aug 17;340(6234):571–574. [PubMed]
  • Cullen BR. Use of eukaryotic expression technology in the functional analysis of cloned genes. Methods Enzymol. 1987;152:684–704. [PubMed]
  • De Jong JJ, De Ronde A, Keulen W, Tersmette M, Goudsmit J. Minimal requirements for the human immunodeficiency virus type 1 V3 domain to support the syncytium-inducing phenotype: analysis by single amino acid substitution. J Virol. 1992 Nov;66(11):6777–6780. [PMC free article] [PubMed]
  • de Jong JJ, Goudsmit J, Keulen W, Klaver B, Krone W, Tersmette M, de Ronde A. Human immunodeficiency virus type 1 clones chimeric for the envelope V3 domain differ in syncytium formation and replication capacity. J Virol. 1992 Feb;66(2):757–765. [PMC free article] [PubMed]
  • Desrosiers RC. The simian immunodeficiency viruses. Annu Rev Immunol. 1990;8:557–578. [PubMed]
  • Desrosiers RC. HIV with multiple gene deletions as a live attenuated vaccine for AIDS. AIDS Res Hum Retroviruses. 1992 Mar;8(3):411–421. [PubMed]
  • Desrosiers RC, Ringler DJ. Use of simian immunodeficiency viruses for AIDS research. Intervirology. 1989;30(6):301–312. [PubMed]
  • Fouchier RA, Groenink M, Kootstra NA, Tersmette M, Huisman HG, Miedema F, Schuitemaker H. Phenotype-associated sequence variation in the third variable domain of the human immunodeficiency virus type 1 gp120 molecule. J Virol. 1992 May;66(5):3183–3187. [PMC free article] [PubMed]
  • Freed EO, Myers DJ. Identification and characterization of fusion and processing domains of the human immunodeficiency virus type 2 envelope glycoprotein. J Virol. 1992 Sep;66(9):5472–5478. [PMC free article] [PubMed]
  • Freed EO, Myers DJ, Risser R. Identification of the principal neutralizing determinant of human immunodeficiency virus type 1 as a fusion domain. J Virol. 1991 Jan;65(1):190–194. [PMC free article] [PubMed]
  • Freed EO, Risser R. Identification of conserved residues in the human immunodeficiency virus type 1 principal neutralizing determinant that are involved in fusion. AIDS Res Hum Retroviruses. 1991 Oct;7(10):807–811. [PubMed]
  • Gardner MB, Luciw PA. Simian immunodeficiency viruses and their relationship to the human immunodeficiency viruses. AIDS. 1988;2 (Suppl 1):S3–10. [PubMed]
  • Goodenow M, Huet T, Saurin W, Kwok S, Sninsky J, Wain-Hobson S. HIV-1 isolates are rapidly evolving quasispecies: evidence for viral mixtures and preferred nucleotide substitutions. J Acquir Immune Defic Syndr. 1989;2(4):344–352. [PubMed]
  • Gorny MK, Conley AJ, Karwowska S, Buchbinder A, Xu JY, Emini EA, Koenig S, Zolla-Pazner S. Neutralization of diverse human immunodeficiency virus type 1 variants by an anti-V3 human monoclonal antibody. J Virol. 1992 Dec;66(12):7538–7542. [PMC free article] [PubMed]
  • Gorny MK, Xu JY, Gianakakos V, Karwowska S, Williams C, Sheppard HW, Hanson CV, Zolla-Pazner S. Production of site-selected neutralizing human monoclonal antibodies against the third variable domain of the human immunodeficiency virus type 1 envelope glycoprotein. Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3238–3242. [PubMed]
  • Goudsmit J, Boucher CA, Meloen RH, Epstein LG, Smit L, van der Hoek L, Bakker M. Human antibody response to a strain-specific HIV-1 gp120 epitope associated with cell fusion inhibition. AIDS. 1988 Jun;2(3):157–164. [PubMed]
  • Goudsmit J, Debouck C, Meloen RH, Smit L, Bakker M, Asher DM, Wolff AV, Gibbs CJ, Jr, Gajdusek DC. Human immunodeficiency virus type 1 neutralization epitope with conserved architecture elicits early type-specific antibodies in experimentally infected chimpanzees. Proc Natl Acad Sci U S A. 1988 Jun;85(12):4478–4482. [PubMed]
  • Grimaila RJ, Fuller BA, Rennert PD, Nelson MB, Hammarskjöld ML, Potts B, Murray M, Putney SD, Gray G. Mutations in the principal neutralization determinant of human immunodeficiency virus type 1 affect syncytium formation, virus infectivity, growth kinetics, and neutralization. J Virol. 1992 Apr;66(4):1875–1883. [PMC free article] [PubMed]
  • Ho DD, Sarngadharan MG, Hirsch MS, Schooley RT, Rota TR, Kennedy RC, Chanh TC, Sato VL. Human immunodeficiency virus neutralizing antibodies recognize several conserved domains on the envelope glycoproteins. J Virol. 1987 Jun;61(6):2024–2028. [PMC free article] [PubMed]
  • Ho SN, Hunt HD, Horton RM, Pullen JK, Pease LR. Site-directed mutagenesis by overlap extension using the polymerase chain reaction. Gene. 1989 Apr 15;77(1):51–59. [PubMed]
  • Holmbäck K, Kusk P, Hulgaard EF, Bugge TH, Scheibel E, Lindhardt BO. Autologous antibody response against the principal neutralizing domain of human immunodeficiency virus type 1 isolated from infected humans. J Virol. 1993 Mar;67(3):1612–1619. [PMC free article] [PubMed]
  • Hoxie JA. Hypothetical assignment of intrachain disulfide bonds for HIV-2 and SIV envelope glycoproteins. AIDS Res Hum Retroviruses. 1991 Jun;7(6):495–499. [PubMed]
  • Hwang SS, Boyle TJ, Lyerly HK, Cullen BR. Identification of the envelope V3 loop as the primary determinant of cell tropism in HIV-1. Science. 1991 Jul 5;253(5015):71–74. [PubMed]
  • Ivanoff LA, Looney DJ, McDanal C, Morris JF, Wong-Staal F, Langlois AJ, Petteway SR, Jr, Matthews TJ. Alteration of HIV-1 infectivity and neutralization by a single amino acid replacement in the V3 loop domain. AIDS Res Hum Retroviruses. 1991 Jul;7(7):595–603. [PubMed]
  • Javaherian K, Langlois AJ, McDanal C, Ross KL, Eckler LI, Jellis CL, Profy AT, Rusche JR, Bolognesi DP, Putney SD, et al. Principal neutralizing domain of the human immunodeficiency virus type 1 envelope protein. Proc Natl Acad Sci U S A. 1989 Sep;86(17):6768–6772. [PubMed]
  • Javaherian K, Langlois AJ, Schmidt S, Kaufmann M, Cates N, Langedijk JP, Meloen RH, Desrosiers RC, Burns DP, Bolognesi DP, et al. The principal neutralization determinant of simian immunodeficiency virus differs from that of human immunodeficiency virus type 1. Proc Natl Acad Sci U S A. 1992 Feb 15;89(4):1418–1422. [PubMed]
  • Johnson PR, Hamm TE, Goldstein S, Kitov S, Hirsch VM. The genetic fate of molecularly cloned simian immunodeficiency virus in experimentally infected macaques. Virology. 1991 Nov;185(1):217–228. [PubMed]
  • Kenealy WR, Matthews TJ, Ganfield MC, Langlois AJ, Waselefsky DM, Petteway SR., Jr Antibodies from human immunodeficiency virus-infected individuals bind to a short amino acid sequence that elicits neutralizing antibodies in animals. AIDS Res Hum Retroviruses. 1989 Apr;5(2):173–182. [PubMed]
  • Kent KA, Rud E, Corcoran T, Powell C, Thiriart C, Collignon C, Stott EJ. Identification of two neutralizing and 8 non-neutralizing epitopes on simian immunodeficiency virus envelope using monoclonal antibodies. AIDS Res Hum Retroviruses. 1992 Jun;8(6):1147–1151. [PubMed]
  • Kestler H, Kodama T, Ringler D, Marthas M, Pedersen N, Lackner A, Regier D, Sehgal P, Daniel M, King N, et al. Induction of AIDS in rhesus monkeys by molecularly cloned simian immunodeficiency virus. Science. 1990 Jun 1;248(4959):1109–1112. [PubMed]
  • Kestler HW, 3rd, Ringler DJ, Mori K, Panicali DL, Sehgal PK, Daniel MD, Desrosiers RC. Importance of the nef gene for maintenance of high virus loads and for development of AIDS. Cell. 1991 May 17;65(4):651–662. [PubMed]
  • Kirchhoff F, Desrosiers RC. A PCR-derived library of random point mutations within the V3 region of simian immunodeficiency virus. PCR Methods Appl. 1993 May;2(4):301–304. [PubMed]
  • Kodama T, Mori K, Kawahara T, Ringler DJ, Desrosiers RC. Analysis of simian immunodeficiency virus sequence variation in tissues of rhesus macaques with simian AIDS. J Virol. 1993 Nov;67(11):6522–6534. [PMC free article] [PubMed]
  • Kuiken CL, de Jong JJ, Baan E, Keulen W, Tersmette M, Goudsmit J. Evolution of the V3 envelope domain in proviral sequences and isolates of human immunodeficiency virus type 1 during transition of the viral biological phenotype. J Virol. 1992 Jul;66(7):4622–4627. [PMC free article] [PubMed]
  • Kusumi K, Conway B, Cunningham S, Berson A, Evans C, Iversen AK, Colvin D, Gallo MV, Coutre S, Shpaer EG, et al. Human immunodeficiency virus type 1 envelope gene structure and diversity in vivo and after cocultivation in vitro. J Virol. 1992 Feb;66(2):875–885. [PMC free article] [PubMed]
  • Laman JD, Schellekens MM, Abacioglu YH, Lewis GK, Tersmette M, Fouchier RA, Langedijk JP, Claassen E, Boersma WJ. Variant-specific monoclonal and group-specific polyclonal human immunodeficiency virus type 1 neutralizing antibodies raised with synthetic peptides from the gp120 third variable domain. J Virol. 1992 Mar;66(3):1823–1831. [PMC free article] [PubMed]
  • McBride BW, Corthals G, Rud E, Kent K, Webster S, Cook N, Cranage MP. Comparison of serum antibody reactivities to a conformational and to linear antigenic sites in the external envelope glycoprotein of simian immunodeficiency virus (SIVmac) induced by infection and vaccination. J Gen Virol. 1993 Jun;74(Pt 6):1033–1041. [PubMed]
  • McCutchan FE, Hegerich PA, Brennan TP, Phanuphak P, Singharaj P, Jugsudee A, Berman PW, Gray AM, Fowler AK, Burke DS. Genetic variants of HIV-1 in Thailand. AIDS Res Hum Retroviruses. 1992 Nov;8(11):1887–1895. [PubMed]
  • Moore JP, Thali M, Jameson BA, Vignaux F, Lewis GK, Poon SW, Charles M, Fung MS, Sun B, Durda PJ, et al. Immunochemical analysis of the gp120 surface glycoprotein of human immunodeficiency virus type 1: probing the structure of the C4 and V4 domains and the interaction of the C4 domain with the V3 loop. J Virol. 1993 Aug;67(8):4785–4796. [PMC free article] [PubMed]
  • Mori K, Ringler DJ, Desrosiers RC. Restricted replication of simian immunodeficiency virus strain 239 in macrophages is determined by env but is not due to restricted entry. J Virol. 1993 May;67(5):2807–2814. [PMC free article] [PubMed]
  • Mori K, Ringler DJ, Kodama T, Desrosiers RC. Complex determinants of macrophage tropism in env of simian immunodeficiency virus. J Virol. 1992 Apr;66(4):2067–2075. [PMC free article] [PubMed]
  • Morrison HG, Kirchhoff F, Desrosiers RC. Evidence for the cooperation of gp120 amino acids 322 and 448 in SIVmac entry. Virology. 1993 Jul;195(1):167–174. [PubMed]
  • Myers G, MacInnes K, Korber B. The emergence of simian/human immunodeficiency viruses. AIDS Res Hum Retroviruses. 1992 Mar;8(3):373–386. [PubMed]
  • O'Brien WA, Koyanagi Y, Namazie A, Zhao JQ, Diagne A, Idler K, Zack JA, Chen IS. HIV-1 tropism for mononuclear phagocytes can be determined by regions of gp120 outside the CD4-binding domain. Nature. 1990 Nov 1;348(6296):69–73. [PubMed]
  • Overbaugh J, Rudensey LM, Papenhausen MD, Benveniste RE, Morton WR. Variation in simian immunodeficiency virus env is confined to V1 and V4 during progression to simian AIDS. J Virol. 1991 Dec;65(12):7025–7031. [PMC free article] [PubMed]
  • Page KA, Stearns SM, Littman DR. Analysis of mutations in the V3 domain of gp160 that affect fusion and infectivity. J Virol. 1992 Jan;66(1):524–533. [PMC free article] [PubMed]
  • Profy AT, Salinas PA, Eckler LI, Dunlop NM, Nara PL, Putney SD. Epitopes recognized by the neutralizing antibodies of an HIV-1-infected individual. J Immunol. 1990 Jun 15;144(12):4641–4647. [PubMed]
  • Regier DA, Desrosiers RC. The complete nucleotide sequence of a pathogenic molecular clone of simian immunodeficiency virus. AIDS Res Hum Retroviruses. 1990 Nov;6(11):1221–1231. [PubMed]
  • Rusche JR, Javaherian K, McDanal C, Petro J, Lynn DL, Grimaila R, Langlois A, Gallo RC, Arthur LO, Fischinger PJ, et al. Antibodies that inhibit fusion of human immunodeficiency virus-infected cells bind a 24-amino acid sequence of the viral envelope, gp120. Proc Natl Acad Sci U S A. 1988 May;85(9):3198–3202. [PubMed]
  • Saag MS, Hahn BH, Gibbons J, Li Y, Parks ES, Parks WP, Shaw GM. Extensive variation of human immunodeficiency virus type-1 in vivo. Nature. 1988 Aug 4;334(6181):440–444. [PubMed]
  • Schulz TF, Reeves JD, Hoad JG, Tailor C, Stephens P, Clements G, Ortlepp S, Page KA, Moore JP, Weiss RA. Effect of mutations in the V3 loop of HIV-1 gp120 on infectivity and susceptibility to proteolytic cleavage. AIDS Res Hum Retroviruses. 1993 Feb;9(2):159–166. [PubMed]
  • Sharpless NE, O'Brien WA, Verdin E, Kufta CV, Chen IS, Dubois-Dalcq M. Human immunodeficiency virus type 1 tropism for brain microglial cells is determined by a region of the env glycoprotein that also controls macrophage tropism. J Virol. 1992 Apr;66(4):2588–2593. [PMC free article] [PubMed]
  • Shioda T, Levy JA, Cheng-Mayer C. Macrophage and T cell-line tropisms of HIV-1 are determined by specific regions of the envelope gp120 gene. Nature. 1991 Jan 10;349(6305):167–169. [PubMed]
  • Simmonds P, Balfe P, Ludlam CA, Bishop JO, Brown AJ. Analysis of sequence diversity in hypervariable regions of the external glycoprotein of human immunodeficiency virus type 1. J Virol. 1990 Dec;64(12):5840–5850. [PMC free article] [PubMed]
  • Skinner MA, Langlois AJ, McDanal CB, McDougal JS, Bolognesi DP, Matthews TJ. Neutralizing antibodies to an immunodominant envelope sequence do not prevent gp120 binding to CD4. J Virol. 1988 Nov;62(11):4195–4200. [PMC free article] [PubMed]
  • Starcich BR, Hahn BH, Shaw GM, McNeely PD, Modrow S, Wolf H, Parks ES, Parks WP, Josephs SF, Gallo RC, et al. Identification and characterization of conserved and variable regions in the envelope gene of HTLV-III/LAV, the retrovirus of AIDS. Cell. 1986 Jun 6;45(5):637–648. [PubMed]
  • Takebe Y, Seiki M, Fujisawa J, Hoy P, Yokota K, Arai K, Yoshida M, Arai N. SR alpha promoter: an efficient and versatile mammalian cDNA expression system composed of the simian virus 40 early promoter and the R-U5 segment of human T-cell leukemia virus type 1 long terminal repeat. Mol Cell Biol. 1988 Jan;8(1):466–472. [PMC free article] [PubMed]
  • Takeuchi Y, Akutsu M, Murayama K, Shimizu N, Hoshino H. Host range mutant of human immunodeficiency virus type 1: modification of cell tropism by a single point mutation at the neutralization epitope in the env gene. J Virol. 1991 Apr;65(4):1710–1718. [PMC free article] [PubMed]
  • Travis BM, Dykers TI, Hewgill D, Ledbetter J, Tsu TT, Hu SL, Lewis JB. Functional roles of the V3 hypervariable region of HIV-1 gp160 in the processing of gp160 and in the formation of syncytia in CD4+ cells. Virology. 1992 Jan;186(1):313–317. [PubMed]
  • Warren RQ, Anderson SA, Nkya WM, Shao JF, Hendrix CW, Melcher GP, Redfield RR, Kennedy RC. Examination of sera from human immunodeficiency virus type 1 (HIV-1)-infected individuals for antibodies reactive with peptides corresponding to the principal neutralizing determinant of HIV-1 gp120 and for in vitro neutralizing activity. J Virol. 1992 Sep;66(9):5210–5215. [PMC free article] [PubMed]
  • Westervelt P, Gendelman HE, Ratner L. Identification of a determinant within the human immunodeficiency virus 1 surface envelope glycoprotein critical for productive infection of primary monocytes. Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3097–3101. [PubMed]
  • Westervelt P, Trowbridge DB, Epstein LG, Blumberg BM, Li Y, Hahn BH, Shaw GM, Price RW, Ratner L. Macrophage tropism determinants of human immunodeficiency virus type 1 in vivo. J Virol. 1992 Apr;66(4):2577–2582. [PMC free article] [PubMed]
  • Wolfs TF, Zwart G, Bakker M, Goudsmit J. HIV-1 genomic RNA diversification following sexual and parenteral virus transmission. Virology. 1992 Jul;189(1):103–110. [PubMed]
  • Wyatt R, Thali M, Tilley S, Pinter A, Posner M, Ho D, Robinson J, Sodroski J. Relationship of the human immunodeficiency virus type 1 gp120 third variable loop to a component of the CD4 binding site in the fourth conserved region. J Virol. 1992 Dec;66(12):6997–7004. [PMC free article] [PubMed]
  • York-Higgins D, Cheng-Mayer C, Bauer D, Levy JA, Dina D. Human immunodeficiency virus type 1 cellular host range, replication, and cytopathicity are linked to the envelope region of the viral genome. J Virol. 1990 Aug;64(8):4016–4020. [PMC free article] [PubMed]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)