Abstract
The importance of the dependence on single amino acids in the V3 region of HIV-1 gp120 was evaluated for virus neutralization and antibody-dependent cellular cytotoxicity (ADCC). Synthetic overlapping 15-mer peptides and a set of omission peptides covering amino acids 301-317 were used. Sera from 29 HIV-1-infected individuals at different stages of disease were tested for neutralization, ADCC and specific IgG reactivity. Six HIV-1 neutralizing monoclonal antibodies (mAb) acted as controls. All mAb reacted with a region (amino acids 304-318) of gp120, previously shown to induce neutralizing antibodies. The amino acids essential for reactivity were identified to be within the sequence GPGR (amino acids 312-315). The importance of this region for occurrence of neutralizing antibodies in infected humans was investigated using the same set of peptides. Out of 29 individuals, 21 were found to have neutralizing antibodies in titres between 100 and 1000. Among the neutralization-positive sera, 17/21 (81%) reacted with amino acids 304-318, compared with only one of eight sera (13%) negative in neutralization. When any of the four amino acids G, P, G or R were deleted, the seroreactivity decreased considerably. The conserved sequence GPGR was therefore considered to be the most important for neutralization in this region in human sera as well. Thus, the conserved sequence GPGR in the V3 region of gp120 is critical for virus neutralization by human HIV-1-specific antibodies.
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Selected References
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- Akerblom L., Hinkula J., Broliden P. A., Mäkitalo B., Fridberger T., Rosen J., Villacres-Eriksson M., Morein B., Wahren B. Neutralizing cross-reactive and non-neutralizing monoclonal antibodies to HIV-1 gp120. AIDS. 1990 Oct;4(10):953–960. doi: 10.1097/00002030-199010000-00002. [DOI] [PubMed] [Google Scholar]
- Albert J., Abrahamsson B., Nagy K., Aurelius E., Gaines H., Nyström G., Fenyö E. M. Rapid development of isolate-specific neutralizing antibodies after primary HIV-1 infection and consequent emergence of virus variants which resist neutralization by autologous sera. AIDS. 1990 Feb;4(2):107–112. doi: 10.1097/00002030-199002000-00002. [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]
- Bolognesi D. P. Natural immunity to HIV and its possible relationship to vaccine strategies. Microbiol Sci. 1988 Aug;5(8):236–241. [PubMed] [Google Scholar]
- Broliden P. A., Ljunggren K., Hinkula J., Norrby E., Akerblom L., Wahren B. A monoclonal antibody to human immunodeficiency virus type 1 which mediates cellular cytotoxicity and neutralization. J Virol. 1990 Feb;64(2):936–940. doi: 10.1128/jvi.64.2.936-940.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Broliden P. A., Morfeldt-Månsson L., Rosen J., Jondal M., Wahren B. Fine specificity of IgG subclass response to group antigens in HIV-1-infected patients. Clin Exp Immunol. 1989 May;76(2):216–221. [PMC free article] [PubMed] [Google Scholar]
- Böttiger B., Karlsson A., Andreasson P. A., Nauclér A., Costa C. M., Norrby E., Biberfeld G. Envelope cross-reactivity between human immunodeficiency virus types 1 and 2 detected by different serological methods: correlation between cross-neutralization and reactivity against the main neutralizing site. J Virol. 1990 Jul;64(7):3492–3499. doi: 10.1128/jvi.64.7.3492-3499.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Böttiger B., Ljunggren K., Karlsson A., Krohn K., Fenyö E. M., Jondal M., Biberfeld G. Neutralizing antibodies in relation to antibody-dependent cellular cytotoxicity-inducing antibodies against human immunodeficiency virus type I. Clin Exp Immunol. 1988 Sep;73(3):339–342. [PMC free article] [PubMed] [Google Scholar]
- Dalgleish A. G., Chanh T. C., Kennedy R. C., Kanda P., Clapham P. R., Weiss R. A. Neutralization of diverse HIV-1 strains by monoclonal antibodies raised against a gp41 synthetic peptide. Virology. 1988 Jul;165(1):209–215. doi: 10.1016/0042-6822(88)90674-5. [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]
- Evans D. J., McKeating J., Meredith J. M., Burke K. L., Katrak K., John A., Ferguson M., Minor P. D., Weiss R. A., Almond J. W. An engineered poliovirus chimaera elicits broadly reactive HIV-1 neutralizing antibodies. Nature. 1989 Jun 1;339(6223):385-8, 340. doi: 10.1038/339385a0. [DOI] [PubMed] [Google Scholar]
- Fultz P. N., Srinivasan A., Greene C. R., Butler D., Swenson R. B., McClure H. M. Superinfection of a chimpanzee with a second strain of human immunodeficiency virus. J Virol. 1987 Dec;61(12):4026–4029. doi: 10.1128/jvi.61.12.4026-4029.1987. [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]
- Ho D. D., Kaplan J. C., Rackauskas I. E., Gurney M. E. Second conserved domain of gp120 is important for HIV infectivity and antibody neutralization. Science. 1988 Feb 26;239(4843):1021–1023. doi: 10.1126/science.2830667. [DOI] [PubMed] [Google Scholar]
- Houghten R. A. General method for the rapid solid-phase synthesis of large numbers of peptides: specificity of antigen-antibody interaction at the level of individual amino acids. Proc Natl Acad Sci U S A. 1985 Aug;82(15):5131–5135. doi: 10.1073/pnas.82.15.5131. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jackson G. G., Perkins J. T., Rubenis M., Paul D. A., Knigge M., Despotes J. C., Spencer P. Passive immunoneutralization of human immunodeficiency virus in patients with advanced AIDS. Lancet. 1988 Sep 17;2(8612):647–652. doi: 10.1016/s0140-6736(88)90468-0. [DOI] [PubMed] [Google Scholar]
- Kenealy W. R., Matthews T. J., Ganfield M. C., Langlois A. J., Waselefsky D. M., Petteway S. R., 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. doi: 10.1089/aid.1989.5.173. [DOI] [PubMed] [Google Scholar]
- Kowalski M., Potz J., Basiripour L., Dorfman T., Goh W. C., Terwilliger E., Dayton A., Rosen C., Haseltine W., Sodroski J. Functional regions of the envelope glycoprotein of human immunodeficiency virus type 1. Science. 1987 Sep 11;237(4820):1351–1355. doi: 10.1126/science.3629244. [DOI] [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]
- Lasky L. A., Groopman J. E., Fennie C. W., Benz P. M., Capon D. J., Dowbenko D. J., Nakamura G. R., Nunes W. M., Renz M. E., Berman P. W. Neutralization of the AIDS retrovirus by antibodies to a recombinant envelope glycoprotein. Science. 1986 Jul 11;233(4760):209–212. doi: 10.1126/science.3014647. [DOI] [PubMed] [Google Scholar]
- Linsley P. S., Ledbetter J. A., Kinney-Thomas E., Hu S. L. Effects of anti-gp120 monoclonal antibodies on CD4 receptor binding by the env protein of human immunodeficiency virus type 1. J Virol. 1988 Oct;62(10):3695–3702. doi: 10.1128/jvi.62.10.3695-3702.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ljunggren K., Broliden P. A., Morfeldt-Månson L., Jondal M., Wahren B. IgG subclass response to HIV in relation to antibody-dependent cellular cytotoxicity at different clinical stages. Clin Exp Immunol. 1988 Sep;73(3):343–347. [PMC free article] [PubMed] [Google Scholar]
- Ljunggren K., Böttiger B., Biberfeld G., Karlson A., Fenyö E. M., Jondal M. Antibody-dependent cellular cytotoxicity-inducing antibodies against human immunodeficiency virus. Presence at different clinical stages. J Immunol. 1987 Oct 1;139(7):2263–2267. [PubMed] [Google Scholar]
- Ljunggren K., Moschese V., Broliden P. A., Giaquinto C., Quinti I., Fenyö E. M., Wahren B., Rossi P., Jondal M. Antibodies mediating cellular cytotoxicity and neutralization correlate with a better clinical stage in children born to human immunodeficiency virus-infected mothers. J Infect Dis. 1990 Feb;161(2):198–202. doi: 10.1093/infdis/161.2.198. [DOI] [PubMed] [Google Scholar]
- Lyerly H. K., Reed D. L., Matthews T. J., Langlois A. J., Ahearne P. A., Petteway S. R., Jr, Weinhold K. J. Anti-GP 120 antibodies from HIV seropositive individuals mediate broadly reactive anti-HIV ADCC. AIDS Res Hum Retroviruses. 1987;3(4):409–422. doi: 10.1089/aid.1987.3.409. [DOI] [PubMed] [Google Scholar]
- Mathiesen T., Broliden P. A., Rosen J., Wahren B. Mapping of IgG subclass and T-cell epitopes on HIV proteins by synthetic peptides. Immunology. 1989 Aug;67(4):453–459. [PMC free article] [PubMed] [Google Scholar]
- Matsushita S., Robert-Guroff M., Rusche J., Koito A., Hattori T., Hoshino H., Javaherian K., Takatsuki K., Putney S. Characterization of a human immunodeficiency virus neutralizing monoclonal antibody and mapping of the neutralizing epitope. J Virol. 1988 Jun;62(6):2107–2114. doi: 10.1128/jvi.62.6.2107-2114.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McKeating J. A., Gow J., Goudsmit J., Pearl L. H., Mulder C., Weiss R. A. Characterization of HIV-1 neutralization escape mutants. AIDS. 1989 Dec;3(12):777–784. doi: 10.1097/00002030-198912000-00001. [DOI] [PubMed] [Google Scholar]
- Meloen R. H., Liskamp R. M., Goudsmit J. Specificity and function of the individual amino acids of an important determinant of human immunodeficiency virus type 1 that induces neutralizing activity. J Gen Virol. 1989 Jun;70(Pt 6):1505–1512. doi: 10.1099/0022-1317-70-6-1505. [DOI] [PubMed] [Google Scholar]
- Modrow S., Hahn B. H., Shaw G. M., Gallo R. C., Wong-Staal F., Wolf H. Computer-assisted analysis of envelope protein sequences of seven human immunodeficiency virus isolates: prediction of antigenic epitopes in conserved and variable regions. J Virol. 1987 Feb;61(2):570–578. doi: 10.1128/jvi.61.2.570-578.1987. [DOI] [PMC free article] [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]
- Papsidero L. D., Sheu M., Ruscetti F. W. Human immunodeficiency virus type 1-neutralizing monoclonal antibodies which react with p17 core protein: characterization and epitope mapping. J Virol. 1989 Jan;63(1):267–272. doi: 10.1128/jvi.63.1.267-272.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Prince A. M., Horowitz B., Baker L., Shulman R. W., Ralph H., Valinsky J., Cundell A., Brotman B., Boehle W., Rey F. Failure of a human immunodeficiency virus (HIV) immune globulin to protect chimpanzees against experimental challenge with HIV. Proc Natl Acad Sci U S A. 1988 Sep;85(18):6944–6948. doi: 10.1073/pnas.85.18.6944. [DOI] [PMC free article] [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]
- Ratner L., Haseltine W., Patarca R., Livak K. J., Starcich B., Josephs S. F., Doran E. R., Rafalski J. A., Whitehorn E. A., Baumeister K. Complete nucleotide sequence of the AIDS virus, HTLV-III. Nature. 1985 Jan 24;313(6000):277–284. doi: 10.1038/313277a0. [DOI] [PubMed] [Google Scholar]
- Robert-Guroff M., Brown M., Gallo R. C. HTLV-III-neutralizing antibodies in patients with AIDS and AIDS-related complex. Nature. 1985 Jul 4;316(6023):72–74. doi: 10.1038/316072a0. [DOI] [PubMed] [Google Scholar]
- Robert-Guroff M., Oleske J. M., Connor E. M., Epstein L. G., Minnefor A. B., Gallo R. C. Relationship between HTLV-III neutralizing antibody and clinical status of pediatric acquired immunodeficiency syndrome (AIDS) and AIDS-related complex cases. Pediatr Res. 1987 Jun;21(6):547–550. doi: 10.1203/00006450-198706000-00008. [DOI] [PubMed] [Google Scholar]
- Rossi P., Moschese V., Broliden P. A., Fundaró C., Quinti I., Plebani A., Giaquinto C., Tovo P. A., Ljunggren K., Rosen J. Presence of maternal antibodies to human immunodeficiency virus 1 envelope glycoprotein gp120 epitopes correlates with the uninfected status of children born to seropositive mothers. Proc Natl Acad Sci U S A. 1989 Oct;86(20):8055–8058. doi: 10.1073/pnas.86.20.8055. [DOI] [PMC free article] [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]
- Skinner M. A., Ting R., Langlois A. J., Weinhold K. J., Lyerly H. K., Javaherian K., Matthews T. J. Characteristics of a neutralizing monoclonal antibody to the HIV envelope glycoprotein. AIDS Res Hum Retroviruses. 1988 Jun;4(3):187–197. doi: 10.1089/aid.1988.4.187. [DOI] [PubMed] [Google Scholar]
- Wahren B., Morfeldt-Månsson L., Biberfeld G., Moberg L., Sönnerborg A., Ljungman P., Werner A., Kurth R., Gallo R., Bolognesi D. Characteristics of the specific cell-mediated immune response in human immunodeficiency virus infection. J Virol. 1987 Jun;61(6):2017–2023. doi: 10.1128/jvi.61.6.2017-2023.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Weber J. N., Clapham P. R., Weiss R. A., Parker D., Roberts C., Duncan J., Weller I., Carne C., Tedder R. S., Pinching A. J. Human immunodeficiency virus infection in two cohorts of homosexual men: neutralising sera and association of anti-gag antibody with prognosis. Lancet. 1987 Jan 17;1(8525):119–122. doi: 10.1016/s0140-6736(87)91964-7. [DOI] [PubMed] [Google Scholar]