Antibody-mediated enhancement of human immunodeficiency virus type 1 infectivity is determined by the structure of gp120 and depends on modulation of the gp120-CCR5 interaction
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作者:
Guillon, C
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机构:Erasmus Univ, Dept Virol, NL-3015 GE Rotterdam, Netherlands
Guillon, C
Schutten, M
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机构:Erasmus Univ, Dept Virol, NL-3015 GE Rotterdam, Netherlands
Schutten, M
Boers, PHM
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机构:Erasmus Univ, Dept Virol, NL-3015 GE Rotterdam, Netherlands
Boers, PHM
Gruters, RA
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机构:Erasmus Univ, Dept Virol, NL-3015 GE Rotterdam, Netherlands
Gruters, RA
Osterhaus, ADME
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机构:Erasmus Univ, Dept Virol, NL-3015 GE Rotterdam, Netherlands
Osterhaus, ADME
机构:
[1] Erasmus Univ, Dept Virol, NL-3015 GE Rotterdam, Netherlands
[2] Ecole Normale Super Lyon, UMR 2142, CNRS, BioMerieux, F-69364 Lyon, France
In this study, we characterized the viral determinants of coreceptor usage in relation to susceptibility to antibody-mediated neutralization or enhancement of infectivity by using chimeras of three highly related human immunodeficiency virus type I (HIV-1) isolates of different phenotypes. We found that the V3 region was the main determinant of antibody-mediated enhancement and coreceptor specificity but that the overall structure of gp120 was also important for these properties. Constructs susceptible to antibody-mediated enhancement preferentially use CCR5 as a coreceptor, in contrast to constructs that were neutralized or not affected. Using monoclonal antibodies directed against CD4 or CCR5, we were able to show that antibody-mediated enhancement was CD4 dependent. Altogether, our results suggest that the modulation of the interaction of gp120 with CCR5 is the mechanism underlying antibody-mediated enhancement of HIV-1 infectivity.
机构:
MIT, Howard Hughes Med Inst, Dept Biol, Whitehead Inst Biomed Res, Cambridge, MA 02142 USAMIT, Howard Hughes Med Inst, Dept Biol, Whitehead Inst Biomed Res, Cambridge, MA 02142 USA
Chan, DC
Kim, PS
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机构:
MIT, Howard Hughes Med Inst, Dept Biol, Whitehead Inst Biomed Res, Cambridge, MA 02142 USAMIT, Howard Hughes Med Inst, Dept Biol, Whitehead Inst Biomed Res, Cambridge, MA 02142 USA
机构:
MIT, Howard Hughes Med Inst, Dept Biol, Whitehead Inst Biomed Res, Cambridge, MA 02142 USAMIT, Howard Hughes Med Inst, Dept Biol, Whitehead Inst Biomed Res, Cambridge, MA 02142 USA
Chan, DC
Kim, PS
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机构:
MIT, Howard Hughes Med Inst, Dept Biol, Whitehead Inst Biomed Res, Cambridge, MA 02142 USAMIT, Howard Hughes Med Inst, Dept Biol, Whitehead Inst Biomed Res, Cambridge, MA 02142 USA