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.
Strain-specific V3 and CD4 binding site autologous HIV-1 neutralizing antibodies select neutralization-resistant viruses
Moody, M. A., Gao, F., Gurley, T. C., Amos, J. D., Kumar, A., Hora, B., Marshall, D. J., Whitesides, J. F., Xia, S-M., Parks, R., Lloyd, K. E., Hwang, K-K., Lu, X., Bonsignori, M., Finzi, A., Vandergrift, N. A., Alam, S. M., Ferrari, G., Shen, X., ... Haynes, B. F. (2015). Strain-specific V3 and CD4 binding site autologous HIV-1 neutralizing antibodies select neutralization-resistant viruses. Cell Host and Microbe, 18(3), 354-362. https://doi.org/10.1016/j.chom.2015.08.006
To contact an RTI author, request a report, or for additional information about publications by our experts, send us your request.
Multifaceted risk for non-suicidal self-injury only versus suicide attempt in a population-based cohort of adults
Long-term effects of a diet supplement containing Cannabis sativa oil and Boswellia serrata in dogs with osteoarthritis following physiotherapy treatments
The effects of exposure to road traffic noise at school on central auditory pathway functional connectivity