Abstract
Human monoclonal antibodies (mAbs) to two contiguous epitopes in the V3 loop of the human immunodeficiency virus type 1 (HIV-1) envelope have shown different effects on three distinct strains of the virus: neutralization, enhancement, or resistance to both processes. Only one amino acid in the mAb epitopes proximal to the crown of the V3 loop was different among these three strains. Substitution of this amino acid in the neutralizable strain with the amino acid of the neutralization-resistant strain or the enhanceable strain resulted in loss of both activities. The conversion of this single amino acid in the neutralization-resistant strain to that of the amino acid found in the neutralization-sensitive strain did not confer the ability for the virus to be neutralized. However, additional changes in neighboring amino acids in the V3 loop succeeded in conferring the neutralization capability. These observations indicate that one antibody species can exert three different effects on various HIV-1 strains. They could explain the emergence of neutralization "escape" variants in the presence of the neutralizing antibodies. Moreover, the results suggest caution in immunization of individuals with the envelope region from one strain since the antibodies induced may show a neutralizing effect against the homologous strain but enhancing effects against other unrelated strains.
Full text
PDF




Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Antibody-dependent enhancement of HIV infection. Lancet. 1988 Jun 4;1(8597):1285–1286. [PubMed] [Google Scholar]
- Castro B. A., Weiss C. D., Wiviott L. D., Levy J. A. Optimal conditions for recovery of the human immunodeficiency virus from peripheral blood mononuclear cells. J Clin Microbiol. 1988 Nov;26(11):2371–2376. doi: 10.1128/jcm.26.11.2371-2376.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cheng-Mayer C., Homsy J., Evans L. A., Levy J. A. Identification of human immunodeficiency virus subtypes with distinct patterns of sensitivity to serum neutralization. Proc Natl Acad Sci U S A. 1988 Apr;85(8):2815–2819. doi: 10.1073/pnas.85.8.2815. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cheng-Mayer C., Rutka J. T., Rosenblum M. L., McHugh T., Stites D. P., Levy J. A. Human immunodeficiency virus can productively infect cultured human glial cells. Proc Natl Acad Sci U S A. 1987 May;84(10):3526–3530. doi: 10.1073/pnas.84.10.3526. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cheng-Mayer C., Weiss C., Seto D., Levy J. A. Isolates of human immunodeficiency virus type 1 from the brain may constitute a special group of the AIDS virus. Proc Natl Acad Sci U S A. 1989 Nov;86(21):8575–8579. doi: 10.1073/pnas.86.21.8575. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gorny M. K., Xu J. Y., Gianakakos V., Karwowska S., Williams C., Sheppard H. W., Hanson C. V., 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. doi: 10.1073/pnas.88.8.3238. [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., Nara P. L., Brooks E., Van Nest G. A., Ott G., Higgins K. W., Dunlop N., Scandella C. J., Eichberg J. W., Steimer K. S. Native but not denatured recombinant human immunodeficiency virus type 1 gp120 generates broad-spectrum neutralizing antibodies in baboons. J Virol. 1992 Jan;66(1):172–182. doi: 10.1128/jvi.66.1.172-182.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Halstead S. B. Pathogenesis of dengue: challenges to molecular biology. Science. 1988 Jan 29;239(4839):476–481. doi: 10.1126/science.3277268. [DOI] [PubMed] [Google Scholar]
- Hoffman A. D., Banapour B., Levy J. A. Characterization of the AIDS-associated retrovirus reverse transcriptase and optimal conditions for its detection in virions. Virology. 1985 Dec;147(2):326–335. doi: 10.1016/0042-6822(85)90135-7. [DOI] [PubMed] [Google Scholar]
- Homsy J., Meyer M., Levy J. A. Serum enhancement of human immunodeficiency virus (HIV) infection correlates with disease in HIV-infected individuals. J Virol. 1990 Apr;64(4):1437–1440. doi: 10.1128/jvi.64.4.1437-1440.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Homsy J., Meyer M., Tateno M., Clarkson S., Levy J. A. The Fc and not CD4 receptor mediates antibody enhancement of HIV infection in human cells. Science. 1989 Jun 16;244(4910):1357–1360. doi: 10.1126/science.2786647. [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]
- Kliks S. C., Nimmanitya S., Nisalak A., Burke D. S. Evidence that maternal dengue antibodies are important in the development of dengue hemorrhagic fever in infants. Am J Trop Med Hyg. 1988 Mar;38(2):411–419. doi: 10.4269/ajtmh.1988.38.411. [DOI] [PubMed] [Google Scholar]
- Kliks S. C., Nisalak A., Brandt W. E., Wahl L., Burke D. S. Antibody-dependent enhancement of dengue virus growth in human monocytes as a risk factor for dengue hemorrhagic fever. Am J Trop Med Hyg. 1989 Apr;40(4):444–451. doi: 10.4269/ajtmh.1989.40.444. [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]
- Levy J. A., Hoffman A. D., Kramer S. M., Landis J. A., Shimabukuro J. M., Oshiro L. S. Isolation of lymphocytopathic retroviruses from San Francisco patients with AIDS. Science. 1984 Aug 24;225(4664):840–842. doi: 10.1126/science.6206563. [DOI] [PubMed] [Google Scholar]
- Liu Z. Q., Wood C., Levy J. A., Cheng-Mayer C. The viral envelope gene is involved in macrophage tropism of a human immunodeficiency virus type 1 strain isolated from brain tissue. J Virol. 1990 Dec;64(12):6148–6153. doi: 10.1128/jvi.64.12.6148-6153.1990. [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]
- Morens D. M., Venkateshan C. N., Halstead S. B. Dengue 4 virus monoclonal antibodies identify epitopes that mediate immune infection enhancement of dengue 2 viruses. J Gen Virol. 1987 Jan;68(Pt 1):91–98. doi: 10.1099/0022-1317-68-1-91. [DOI] [PubMed] [Google Scholar]
- Nara P. L., Smit L., Dunlop N., Hatch W., Merges M., Waters D., Kelliher J., Gallo R. C., Fischinger P. J., Goudsmit J. Emergence of viruses resistant to neutralization by V3-specific antibodies in experimental human immunodeficiency virus type 1 IIIB infection of chimpanzees. J Virol. 1990 Aug;64(8):3779–3791. doi: 10.1128/jvi.64.8.3779-3791.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Olsen C. W., Corapi W. V., Ngichabe C. K., Baines J. D., Scott F. W. Monoclonal antibodies to the spike protein of feline infectious peritonitis virus mediate antibody-dependent enhancement of infection of feline macrophages. J Virol. 1992 Feb;66(2):956–965. doi: 10.1128/jvi.66.2.956-965.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Robinson W. E., Jr, Montefiori D. C., Mitchell W. M. Antibody-dependent enhancement of human immunodeficiency virus type 1 infection. Lancet. 1988 Apr 9;1(8589):790–794. doi: 10.1016/s0140-6736(88)91657-1. [DOI] [PubMed] [Google Scholar]
- Robinson W. E., Jr, Montefiori D. C., Mitchell W. M., Prince A. M., Alter H. J., Dreesman G. R., Eichberg J. W. Antibody-dependent enhancement of human immunodeficiency virus type 1 (HIV-1) infection in vitro by serum from HIV-1-infected and passively immunized chimpanzees. Proc Natl Acad Sci U S A. 1989 Jun;86(12):4710–4714. doi: 10.1073/pnas.86.12.4710. [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]
- Sanchez-Pescador R., Power M. D., Barr P. J., Steimer K. S., Stempien M. M., Brown-Shimer S. L., Gee W. W., Renard A., Randolph A., Levy J. A. Nucleotide sequence and expression of an AIDS-associated retrovirus (ARV-2). Science. 1985 Feb 1;227(4686):484–492. doi: 10.1126/science.2578227. [DOI] [PubMed] [Google Scholar]
- Shioda T., Levy J. A., 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. doi: 10.1038/349167a0. [DOI] [PubMed] [Google Scholar]
- Shioda T., Levy J. A., Cheng-Mayer C. Small amino acid changes in the V3 hypervariable region of gp120 can affect the T-cell-line and macrophage tropism of human immunodeficiency virus type 1. Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9434–9438. doi: 10.1073/pnas.89.20.9434. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Takeda A., Ennis F. A. FcR-mediated enhancement of HIV-1 infection by antibody. AIDS Res Hum Retroviruses. 1990 Aug;6(8):999–1004. doi: 10.1089/aid.1990.6.999. [DOI] [PubMed] [Google Scholar]
- Takeda A., Tuazon C. U., Ennis F. A. Antibody-enhanced infection by HIV-1 via Fc receptor-mediated entry. Science. 1988 Oct 28;242(4878):580–583. doi: 10.1126/science.2972065. [DOI] [PubMed] [Google Scholar]
- Weiss R. A., Clapham P. R., Weber J. N., Dalgleish A. G., Lasky L. A., Berman P. W. Variable and conserved neutralization antigens of human immunodeficiency virus. Nature. 1986 Dec 11;324(6097):572–575. doi: 10.1038/324572a0. [DOI] [PubMed] [Google Scholar]