Strain-Specific V3 and CD4 Binding Site Autologous HIV-1 Neutralizing Antibodies Select Neutralization-Resistant Viruses.

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Moody, MA; Gao, F; Gurley, TC; Amos, JD; Kumar, A; Hora, B; Marshall, DJ; Whitesides, JF; Xia, S-M; Parks, R; Lloyd, KE; Hwang, K-K; Lu, X; Bonsignori, M; Finzi, A; Vandergrift, NA; Alam, SM; Ferrari, G; Shen, X; Tomaras, GD; Kamanga, G; Cohen, MS; Sam, NE; Kapiga, S; Gray, ES; Tumba, NL; Morris, L; Zolla-Pazner, S; Gorny, MK; Mascola, JR; Hahn, BH; Shaw, GM; Sodroski, JG; Liao, H-X; Montefiori, DC; Hraber, PT; Korber, BT; Haynes, BF

Published Date

  • September 2015

Published In

Volume / Issue

  • 18 / 3

Start / End Page

  • 354 - 362

PubMed ID

  • 26355218

Electronic International Standard Serial Number (EISSN)

  • 1934-6069

International Standard Serial Number (ISSN)

  • 1931-3128

Digital Object Identifier (DOI)

  • 10.1016/j.chom.2015.08.006

Language

  • eng