Resistance to V3-directed neutralization caused by an N-linked oligosaccharide depends on the quaternary structure of the HIV-1 envelope oligomer

被引:74
作者
Schonning, K
Jansson, B
Olofsson, S
Nielsen, JO
Hansen, JES
机构
[1] HVIDOVRE UNIV HOSP,DEPT 144,INFECT DIS LAB,DK-2650 HVIDOVRE,DENMARK
[2] GOTHENBURG UNIV,DEPT CLIN VIROL,S-41346 GOTHENBURG,SWEDEN
关键词
D O I
10.1006/viro.1996.0173
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
A conserved N-glycan present within the V3 loop of gp120 modulates the sensitivity to neutralization by antibodies directed to the Vs loop. A glycan-deficient mutant of HIVLAI, designated HIVA308, displayed a 100-fold increase in sensitivity to neutralization by anti-V3 MAb NEA-9205 compared to wild-type HIVLAI. This difference in sensitivity was not caused by an alteration of the antibody binding site itself, as NEA-9205 had equal affinity for both wild-type and mutant monomeric gp120, In contrast, virion-associated wild-type gp120 was immunoprecipitated less efficiently with NEA-9205 than virion-associated mutant gp120. This difference was completely abrogated, if immunoprecipitation were carried out in the presence of detergent. Furthermore, treatment of virion preparations with detergent exposed the C-terminal D7324 epitope, which is inaccessible on virion-associated gp120 but readily accessible on monomeric, soluble gp120. Finally, both wild-type and mutant monomeric, soluble gp120 were precipitated equally efficiently by NEA-9205 in the absence of detergent. Thus, the NEA-9205 epitope was readily accessible on monomeric gp120 regardless of the presence of the N-306-glycan, and inaccessibility of the NEA-9205 epitope imparted by the N-306-glycan was observed only on the intact envelope oligomer. (C) 1996 Academic Press, Inc.
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页码:134 / 140
页数:7
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