Amino Acid Changes in the HIV-1 gp41 Membrane Proximal Region Control Virus Neutralization Sensitivity

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Amino Acid Changes in the HIV-1 gp41 Membrane Proximal Region Control Virus Neutralization Sensitivity

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Title: Amino Acid Changes in the HIV-1 gp41 Membrane Proximal Region Control Virus Neutralization Sensitivity
Author: Bradley, Todd; Trama, Ashley; Tumba, Nancy; Gray, Elin; Lu, Xiaozhi; Madani, Navid; Jahanbakhsh, Fatemeh; Eaton, Amanda; Xia, Shi-Mao; Parks, Robert; Lloyd, Krissey E.; Sutherland, Laura L.; Scearce, Richard M.; Bowman, Cindy M.; Barnett, Susan; Abdool-Karim, Salim S.; Boyd, Scott D.; Melillo, Bruno; Smith, Amos B.; Sodroski, Joseph; Kepler, Thomas B.; Alam, S.Munir; Gao, Feng; Bonsignori, Mattia; Liao, Hua-Xin; Moody, M. Anthony; Montefiori, David; Santra, Sampa; Morris, Lynn; Haynes, Barton F.

Note: Order does not necessarily reflect citation order of authors.

Citation: Bradley, 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.
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Abstract: Most 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.
Published Version: doi:10.1016/j.ebiom.2016.08.045
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5078591/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:29626216
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