AEGiS-08IAC: Resistance of HIV-1 to broadly neutralizing sera linked to V3-antibody resistance due to distant site mutations.

8th International AIDS Conference


Amsterdam, Netherlands — July 19-24, 1992

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Resistance of HIV-1 to broadly neutralizing sera linked to V3-antibody resistance due to distant site mutations.

Int Conf AIDS 1992 Jul 19-24; 8:We45 (abstract no. WeA 1001)
Back N, Smit L, Nara PL, Ramautarsing C, Tersmette M, Goudsmit J;

OBJECTIVES: To analyze the mechanism of neutralization resistance of a V32 HIV-1 strain, recovered from an HIV-1 IIIB infected chimpanzee.

METHODS: Neutralization of the resistant virus V32 by a panel of V3 antibodies and human sera was investigated. Effects of virus stock preparation on neutralization was tested with a panel of plaque-purified clones. The V3 sequences of these clones were analyzed and the binding of V3 MAbs to the neutralization sensitive HX10 clone and to the resistant clones were compared in a gp120 capture ELISA. Three molecularly cloned viruses were produced chimeric for the gp120 coding region of the resistant biological clones and tested for neutralization capacity.

RESULTS: Passage of HIV-1 IIIB in a chimpanzee yielded, after 32 weeks, a virus isolate (V32) resistant to neutralization by V3-specific monoclonal and polyclonal sera, although these antibodies bound to resistant and sensitive viruses with comparable affinity. Broadly neutralizing sera with gp120-CD4 blocking antibodies but without homologous V3-specific antibodies did not neutralize the V32 isolate but did neutralize another isolate (HX10) with an identical V3 epitope (lambda BH10), suggesting a distinction in sensitivity to V3 antibodies. Biological cloning of the V32 isolate, by limiting dilution and plaque purification, confirmed the presence of virus clones that simultaneously resisted neutralization by V3-specific and broadly neutralizing sera. Subsequently, in two of the three chimaeric gp120 viruses the determinants conferring the neutralizing antibody resistant phenotype were localized within the external envelope coding region.

CONCLUSIONS: The explanation for the resistant phenotype is not the differences in V3 regions, nor the shedding of gp120 or the various cell lines stock preparations or the V3 binding affinities, but the mutations present in the external envelope giving viruses the characteristics to resist neutralization by broadly neutralizing and V3-specific sera.

Keywords: AEGIS, HIV-1, Aluminum Hydroxide, Antigens, CD4, Mutation, Pan troglodytes, Antibodies, Monoclonal, Epitopes, Link, Animal, Human, genetics, ICA8KWDaegis,hiv-1,aluminumhydroxide,antigens,cd4,mutation,pantroglodytes,antibodies,monoclonal,epitopes,link,animal,human,genetics,ica8
920719
WeA1001

Copyright © 1992 - International AIDS Society (IAS). Reproduction of this abstract (other than one copy for personal reference) must be cleared through the IAS.