Bradley, ToddTrama, AshleyTumba, NancyGray, ElinLu, XiaozhiMadani, NavidJahanbakhsh, FatemehEaton, AmandaXia, Shi-MaoParks, RobertLloyd, Krissey E.Sutherland, Laura L.Scearce, Richard M.Bowman, Cindy M.Barnett, SusanAbdool-Karim, Salim S.Boyd, Scott D.Melillo, BrunoSmith, Amos B.Sodroski, JosephKepler, Thomas B.Alam, S.MunirGao, FengBonsignori, MattiaLiao, Hua-XinMoody, M. AnthonyMontefiori, DavidSantra, SampaMorris, LynnHaynes, Barton F.2016-12-022016Bradley, T., A. Trama, N. Tumba, E. Gray, X. Lu, N. Madani, F. Jahanbakhsh, et al. 2016. “Amino Acid Changes in the HIV-1 gp41 Membrane Proximal Region Control Virus Neutralization Sensitivity.” EBioMedicine 12 (1): 196-207. doi:10.1016/j.ebiom.2016.08.045. http://dx.doi.org/10.1016/j.ebiom.2016.08.045.2352-3964http://nrs.harvard.edu/urn-3:HUL.InstRepos:29626216Most HIV-1 vaccines elicit neutralizing antibodies that are active against highly sensitive (tier-1) viruses or rare cases of vaccine-matched neutralization-resistant (tier-2) viruses, but no vaccine has induced antibodies that can broadly neutralize heterologous tier-2 viruses. In this study, we isolated antibodies from an HIV-1-infected individual that targeted the gp41 membrane-proximal external region (MPER) that may have selected single-residue changes in viral variants in the MPER that resulted in neutralization sensitivity to antibodies targeting distal epitopes on the HIV-1 Env. Similarly, a single change in the MPER in a second virus from another infected-individual also conferred enhanced neutralization sensitivity. These gp41 single-residue changes thus transformed tier-2 viruses into tier-1 viruses that were sensitive to vaccine-elicited tier-1 neutralizing antibodies. These data demonstrate that Env amino acid changes within the MPER bnAb epitope of naturally-selected escape viruses can increase neutralization sensitivity to multiple types of neutralizing antibodies, and underscore the critical importance of the MPER for maintaining the integrity of the tier-2 HIV-1 trimer.en-USJournal Article2016-12-0210.1016/j.ebiom.2016.08.045