期刊
CELL HOST & MICROBE
卷 18, 期 3, 页码 354-362出版社
CELL PRESS
DOI: 10.1016/j.chom.2015.08.006
关键词
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资金
- Bill and Melinda Gates Foundation
- Center for HIV/AIDS Vaccine Immunology (CHAVI) [U19 AI067854]
- Center for HIV/AIDS Vaccine Immunology-Immunogen Discovery grant (CHAVI-ID) [UM1 AI100645]
- CAVD [OPP1032325]
- Duke Center for AIDS Research Flow Cytometry and Virology cores (CFAR) [P30-AI-64518]
- NIH [P01 AI 100151]
- Department of Veterans Affairs
The third variable (V3) loop and the CD4 binding site (CD4bs) of the HIV-1 envelope are frequently targeted by neutralizing antibodies (nAbs) in infected individuals. In chronic infection, HIV-1 escape mutants repopulate the plasma, and V3 and CD4bs nAbs emerge that can neutralize heterologous tier 1 easy-to-neutralize but not tier 2 difficult-to-neutralize HIV-1 isolates. However, neutralization sensitivity of autologous plasma viruses to this type of nAb response has not been studied. We describe the development and evolution in vivo of antibodies distinguished by their target specificity for V3 and CD4bs epitopes on autologous tier 2 viruses but not on heterologous tier 2 viruses. A surprisingly high fraction of autologous circulating viruses was sensitive to these antibodies. These findings demonstrate a role for V3 and CD4bs anti-bodies in constraining the native envelope trimer in vivo to a neutralization-resistant phenotype, explaining why HIV-1 transmission generally occurs by tier 2 neutralization-resistant viruses.
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