| Literature DB >> 26355218 |
M Anthony Moody1, Feng Gao2, Thaddeus C Gurley3, Joshua D Amos3, Amit Kumar3, Bhavna Hora3, Dawn J Marshall3, John F Whitesides3, Shi-Mao Xia3, Robert Parks3, Krissey E Lloyd3, Kwan-Ki Hwang3, Xiaozhi Lu3, Mattia Bonsignori3, Andrés Finzi4, Nathan A Vandergrift5, S Munir Alam6, Guido Ferrari7, Xiaoying Shen3, Georgia D Tomaras8, Gift Kamanga9, Myron S Cohen10, Noel E Sam11, Saidi Kapiga12, Elin S Gray13, Nancy L Tumba13, Lynn Morris14, Susan Zolla-Pazner15, Miroslaw K Gorny16, John R Mascola17, Beatrice H Hahn18, George M Shaw18, Joseph G Sodroski19, Hua-Xin Liao5, David C Montefiori20, Peter T Hraber21, Bette T Korber21, Barton F Haynes22.
Abstract
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 antibodies 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.Entities:
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Year: 2015 PMID： 26355218 PMCID： PMC4567706 DOI： 10.1016/j.chom.2015.08.006
Source DB: PubMed Journal: Cell Host Microbe ISSN： 1931-3128 Impact factor: 21.023