Strain-Specific V3 and CD4 Binding Site Autologous HIV-1 Neutralizing Antibodies Select Neutralization-Resistant Viruses.
Journal Article (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
- Alam, S. Munir
- Ferrari, Guido
- Gao, Feng
- Haynes, Barton Ford
- Liao, Hua-Xin
- Montefiori, David Charles
- Moody, Michael Anthony
- Tomaras, Georgia Doris
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 9, 2015
Published In
Volume / Issue
- 18 / 3
Start / End Page
- 354 - 362
PubMed ID
- 26355218
Pubmed Central ID
- PMC4567706
Electronic International Standard Serial Number (EISSN)
- 1934-6069
Digital Object Identifier (DOI)
- 10.1016/j.chom.2015.08.006
Language
- eng
Conference Location
- United States