Abstract
To identify the principal neutralization determinant (PND) of simian immunodeficiency virus (SIV), antisera were generated using recombinant gp110 [the SIV analog of the human immunodeficiency virus type 1 (HIV-1) external envelope glycoprotein, gp120], gp140, several large recombinant and proteolytic envelope fragments, and synthetic peptides of the SIVmac251 isolate. When purified under conditions that retain its native structure, gp110 bound CD4 and elicited antisera that neutralized SIVmac251 with high titer. Native gp110 also completely inhibited neutralizing antibody in sera from SIVmac251-infected macaques. In contrast, denatured gp110 and gp140, large envelope fragments, and synthetic peptides (including peptides analogous to the HIV-1 PND) elicited very low or undetectable neutralizing antibody titers and did not inhibit neutralizing antibody in infected macaque sera. Enzymatically deglycosylated gp110 efficiently absorbed neutralizing antibodies from macaque sera, showing that neutralizing antibodies primarily bind the protein backbone. A 45-kDa protease digest product, mapping to the carboxyl-terminal third of gp110, also completely absorbed neutralizing antibodies from infected macaque sera. These results show that the PND(s) of this SIV isolate depends on the native conformation and that linear peptides corresponding to the V3 loop of SIV envelope, in contrast to that of HIV-1, do not elicit neutralizing antibody. This may affect the usefulness of SIVmac for evaluating HIV-1 envelope vaccine approaches that rely on eliciting neutralizing antibody.
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- Acharya R., Fry E., Stuart D., Fox G., Rowlands D., Brown F. The three-dimensional structure of foot-and-mouth disease virus at 2.9 A resolution. Nature. 1989 Feb 23;337(6209):709–716. doi: 10.1038/337709a0. [DOI] [PubMed] [Google Scholar]
- Berman P. W., Gregory T. J., Riddle L., Nakamura G. R., Champe M. A., Porter J. P., Wurm F. M., Hershberg R. D., Cobb E. K., Eichberg J. W. Protection of chimpanzees from infection by HIV-1 after vaccination with recombinant glycoprotein gp120 but not gp160. Nature. 1990 Jun 14;345(6276):622–625. doi: 10.1038/345622a0. [DOI] [PubMed] [Google Scholar]
- Burns D. P., Desrosiers R. C. Selection of genetic variants of simian immunodeficiency virus in persistently infected rhesus monkeys. J Virol. 1991 Apr;65(4):1843–1854. doi: 10.1128/jvi.65.4.1843-1854.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Daniel M. D., Letvin N. L., Sehgal P. K., Hunsmann G., Schmidt D. K., King N. W., Desrosiers R. C. Long-term persistent infection of macaque monkeys with the simian immunodeficiency virus. J Gen Virol. 1987 Dec;68(Pt 12):3183–3189. doi: 10.1099/0022-1317-68-12-3183. [DOI] [PubMed] [Google Scholar]
- Desrosiers R. C., Letvin N. L. Animal models for acquired immunodeficiency syndrome. Rev Infect Dis. 1987 May-Jun;9(3):438–446. doi: 10.1093/clinids/9.3.438. [DOI] [PubMed] [Google Scholar]
- Desrosiers R. C. The simian immunodeficiency viruses. Annu Rev Immunol. 1990;8:557–578. doi: 10.1146/annurev.iy.08.040190.003013. [DOI] [PubMed] [Google Scholar]
- Desrosiers R. C., Wyand M. S., Kodama T., Ringler D. J., Arthur L. O., Sehgal P. K., Letvin N. L., King N. W., Daniel M. D. Vaccine protection against simian immunodeficiency virus infection. Proc Natl Acad Sci U S A. 1989 Aug;86(16):6353–6357. doi: 10.1073/pnas.86.16.6353. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dowbenko D., Nakamura G., Fennie C., Shimasaki C., Riddle L., Harris R., Gregory T., Lasky L. Epitope mapping of the human immunodeficiency virus type 1 gp120 with monoclonal antibodies. J Virol. 1988 Dec;62(12):4703–4711. doi: 10.1128/jvi.62.12.4703-4711.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Emini E. A., Nara P. L., Schleif W. A., Lewis J. A., Davide J. P., Lee D. R., Kessler J., Conley S., Matsushita S., Putney S. D. Antibody-mediated in vitro neutralization of human immunodeficiency virus type 1 abolishes infectivity for chimpanzees. J Virol. 1990 Aug;64(8):3674–3678. doi: 10.1128/jvi.64.8.3674-3678.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fennie C., Lasky L. A. Model for intracellular folding of the human immunodeficiency virus type 1 gp120. J Virol. 1989 Feb;63(2):639–646. doi: 10.1128/jvi.63.2.639-646.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Franchini G., Gurgo C., Guo H. G., Gallo R. C., Collalti E., Fargnoli K. A., Hall L. F., Wong-Staal F., Reitz M. S., Jr Sequence of simian immunodeficiency virus and its relationship to the human immunodeficiency viruses. Nature. 1987 Aug 6;328(6130):539–543. doi: 10.1038/328539a0. [DOI] [PubMed] [Google Scholar]
- Gardner M. B., Luciw P. A. Animal models of AIDS. FASEB J. 1989 Dec;3(14):2593–2606. doi: 10.1096/fasebj.3.14.2556312. [DOI] [PubMed] [Google Scholar]
- Gardner M. B. Vaccination against SIV infection and disease. AIDS Res Hum Retroviruses. 1990 Jul;6(7):835–846. doi: 10.1089/aid.1990.6.835. [DOI] [PubMed] [Google Scholar]
- Geysen H. M., Barteling S. J., Meloen R. H. Small peptides induce antibodies with a sequence and structural requirement for binding antigen comparable to antibodies raised against the native protein. Proc Natl Acad Sci U S A. 1985 Jan;82(1):178–182. doi: 10.1073/pnas.82.1.178. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Geysen H. M., Meloen R. H., Barteling S. J. Use of peptide synthesis to probe viral antigens for epitopes to a resolution of a single amino acid. Proc Natl Acad Sci U S A. 1984 Jul;81(13):3998–4002. doi: 10.1073/pnas.81.13.3998. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Girard M., Kieny M. P., Pinter A., Barre-Sinoussi F., Nara P., Kolbe H., Kusumi K., Chaput A., Reinhart T., Muchmore E. Immunization of chimpanzees confers protection against challenge with human immunodeficiency virus. Proc Natl Acad Sci U S A. 1991 Jan 15;88(2):542–546. doi: 10.1073/pnas.88.2.542. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Goudsmit J., Debouck C., Meloen R. H., Smit L., Bakker M., Asher D. M., Wolff A. V., Gibbs C. J., Jr, Gajdusek D. C. 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. doi: 10.1073/pnas.85.12.4478. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Haigwood N. L., Shuster J. R., Moore G. K., Lee H., Skiles P. V., Higgins K. W., Barr P. J., George-Nascimento C., Steimer K. S. Importance of hypervariable regions of HIV-1 gp120 in the generation of virus neutralizing antibodies. AIDS Res Hum Retroviruses. 1990 Jul;6(7):855–869. doi: 10.1089/aid.1990.6.855. [DOI] [PubMed] [Google Scholar]
- Ho D. D., McKeating J. A., Li X. L., Moudgil T., Daar E. S., Sun N. C., Robinson J. E. Conformational epitope on gp120 important in CD4 binding and human immunodeficiency virus type 1 neutralization identified by a human monoclonal antibody. J Virol. 1991 Jan;65(1):489–493. doi: 10.1128/jvi.65.1.489-493.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hogle J. M., Chow M., Filman D. J. Three-dimensional structure of poliovirus at 2.9 A resolution. Science. 1985 Sep 27;229(4720):1358–1365. doi: 10.1126/science.2994218. [DOI] [PubMed] [Google Scholar]
- Javaherian K., Langlois A. J., McDanal C., Ross K. L., Eckler L. I., Jellis C. L., Profy A. T., Rusche J. R., Bolognesi D. P., Putney S. D. 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. doi: 10.1073/pnas.86.17.6768. [DOI] [PMC free article] [PubMed] [Google Scholar]
- LaRosa G. J., Davide J. P., Weinhold K., Waterbury J. A., Profy A. T., Lewis J. A., Langlois A. J., Dreesman G. R., Boswell R. N., Shadduck P. Conserved sequence and structural elements in the HIV-1 principal neutralizing determinant. Science. 1990 Aug 24;249(4971):932–935. doi: 10.1126/science.2392685. [DOI] [PubMed] [Google Scholar]
- Langlois A. J., Weinhold K. J., Matthews T. J., Bolognesi D. P. In vitro assays for detecting neutralizing and fusion-inhibiting antibodies to SIVMAC251. AIDS Res Hum Retroviruses. 1991 Aug;7(8):713–720. doi: 10.1089/aid.1991.7.713. [DOI] [PubMed] [Google Scholar]
- Luckow V. A., Summers M. D. High level expression of nonfused foreign genes with Autographa californica nuclear polyhedrosis virus expression vectors. Virology. 1989 May;170(1):31–39. doi: 10.1016/0042-6822(89)90348-6. [DOI] [PubMed] [Google Scholar]
- Matthews T. J., Weinhold K. J., Lyerly H. K., Langlois A. J., Wigzell H., Bolognesi D. P. Interaction between the human T-cell lymphotropic virus type IIIB envelope glycoprotein gp120 and the surface antigen CD4: role of carbohydrate in binding and cell fusion. Proc Natl Acad Sci U S A. 1987 Aug;84(15):5424–5428. doi: 10.1073/pnas.84.15.5424. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McDougal J. S., Nicholson J. K., Cross G. D., Cort S. P., Kennedy M. S., Mawle A. C. Binding of the human retrovirus HTLV-III/LAV/ARV/HIV to the CD4 (T4) molecule: conformation dependence, epitope mapping, antibody inhibition, and potential for idiotypic mimicry. J Immunol. 1986 Nov 1;137(9):2937–2944. [PubMed] [Google Scholar]
- Murphey-Corb M., Martin L. N., Davison-Fairburn B., Montelaro R. C., Miller M., West M., Ohkawa S., Baskin G. B., Zhang J. Y., Putney S. D. A formalin-inactivated whole SIV vaccine confers protection in macaques. Science. 1989 Dec 8;246(4935):1293–1297. doi: 10.1126/science.2555923. [DOI] [PubMed] [Google Scholar]
- Palker T. J., Clark M. E., Langlois A. J., Matthews T. J., Weinhold K. J., Randall R. R., Bolognesi D. P., Haynes B. F. Type-specific neutralization of the human immunodeficiency virus with antibodies to env-encoded synthetic peptides. Proc Natl Acad Sci U S A. 1988 Mar;85(6):1932–1936. doi: 10.1073/pnas.85.6.1932. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Posner M. R., Hideshima T., Cannon T., Mukherjee M., Mayer K. H., Byrn R. A. An IgG human monoclonal antibody that reacts with HIV-1/GP120, inhibits virus binding to cells, and neutralizes infection. J Immunol. 1991 Jun 15;146(12):4325–4332. [PubMed] [Google Scholar]
- Profy A. T., Salinas P. A., Eckler L. I., Dunlop N. M., Nara P. L., Putney S. D. Epitopes recognized by the neutralizing antibodies of an HIV-1-infected individual. J Immunol. 1990 Jun 15;144(12):4641–4647. [PubMed] [Google Scholar]
- Putkonen P., Thorstensson R., Ghavamzadeh L., Albert J., Hild K., Biberfeld G., Norrby E. Prevention of HIV-2 and SIVsm infection by passive immunization in cynomolgus monkeys. Nature. 1991 Aug 1;352(6334):436–438. doi: 10.1038/352436a0. [DOI] [PubMed] [Google Scholar]
- Putney S. D., Matthews T. J., Robey W. G., Lynn D. L., Robert-Guroff M., Mueller W. T., Langlois A. J., Ghrayeb J., Petteway S. R., Jr, Weinhold K. J. HTLV-III/LAV-neutralizing antibodies to an E. coli-produced fragment of the virus envelope. Science. 1986 Dec 12;234(4782):1392–1395. doi: 10.1126/science.2431482. [DOI] [PubMed] [Google Scholar]
- Robey W. G., Arthur L. O., Matthews T. J., Langlois A., Copeland T. D., Lerche N. W., Oroszlan S., Bolognesi D. P., Gilden R. V., Fischinger P. J. Prospect for prevention of human immunodeficiency virus infection: purified 120-kDa envelope glycoprotein induces neutralizing antibody. Proc Natl Acad Sci U S A. 1986 Sep;83(18):7023–7027. doi: 10.1073/pnas.83.18.7023. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rossmann M. G., Arnold E., Erickson J. W., Frankenberger E. A., Griffith J. P., Hecht H. J., Johnson J. E., Kamer G., Luo M., Mosser A. G. Structure of a human common cold virus and functional relationship to other picornaviruses. Nature. 1985 Sep 12;317(6033):145–153. doi: 10.1038/317145a0. [DOI] [PubMed] [Google Scholar]
- Rusche J. R., Javaherian K., McDanal C., Petro J., Lynn D. L., Grimaila R., Langlois A., Gallo R. C., Arthur L. O., Fischinger P. J. 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. doi: 10.1073/pnas.85.9.3198. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rusche J. R., Lynn D. L., Robert-Guroff M., Langlois A. J., Lyerly H. K., Carson H., Krohn K., Ranki A., Gallo R. C., Bolognesi D. P. Humoral immune response to the entire human immunodeficiency virus envelope glycoprotein made in insect cells. Proc Natl Acad Sci U S A. 1987 Oct;84(19):6924–6928. doi: 10.1073/pnas.84.19.6924. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sutjipto S., Pedersen N. C., Miller C. J., Gardner M. B., Hanson C. V., Gettie A., Jennings M., Higgins J., Marx P. A. Inactivated simian immunodeficiency virus vaccine failed to protect rhesus macaques from intravenous or genital mucosal infection but delayed disease in intravenously exposed animals. J Virol. 1990 May;64(5):2290–2297. doi: 10.1128/jvi.64.5.2290-2297.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tilley S. A., Honnen W. J., Racho M. E., Hilgartner M., Pinter A. A human monoclonal antibody against the CD4-binding site of HIV1 gp120 exhibits potent, broadly neutralizing activity. Res Virol. 1991 Jul-Aug;142(4):247–259. doi: 10.1016/0923-2516(91)90010-z. [DOI] [PubMed] [Google Scholar]