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

Publication ,  Journal Article
Bradley, T; Trama, A; Tumba, N; Gray, E; Lu, X; Madani, N; Jahanbakhsh, F; Eaton, A; Xia, S-M; Parks, R; Lloyd, KE; Sutherland, LL; Boyd, SD ...
Published in: EBioMedicine
October 2016

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.

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Published In

EBioMedicine

DOI

EISSN

2352-3964

Publication Date

October 2016

Volume

12

Start / End Page

196 / 207

Location

Netherlands

Related Subject Headings

  • Protein Interaction Domains and Motifs
  • Neutralization Tests
  • Mutation
  • Macaca mulatta
  • Immunization
  • Humans
  • HIV-1
  • HIV Infections
  • HIV Envelope Protein gp41
  • HIV Envelope Protein gp120
 

Citation

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Bradley, T., Trama, A., Tumba, N., Gray, E., Lu, X., Madani, N., … Haynes, B. F. (2016). Amino Acid Changes in the HIV-1 gp41 Membrane Proximal Region Control Virus Neutralization Sensitivity. EBioMedicine, 12, 196–207. https://doi.org/10.1016/j.ebiom.2016.08.045
Bradley, Todd, Ashley Trama, Nancy Tumba, Elin Gray, Xiaozhi Lu, Navid Madani, Fatemeh Jahanbakhsh, et al. “Amino Acid Changes in the HIV-1 gp41 Membrane Proximal Region Control Virus Neutralization Sensitivity.EBioMedicine 12 (October 2016): 196–207. https://doi.org/10.1016/j.ebiom.2016.08.045.
Bradley T, Trama A, Tumba N, Gray E, Lu X, Madani N, et al. Amino Acid Changes in the HIV-1 gp41 Membrane Proximal Region Control Virus Neutralization Sensitivity. EBioMedicine. 2016 Oct;12:196–207.
Bradley, Todd, et al. “Amino Acid Changes in the HIV-1 gp41 Membrane Proximal Region Control Virus Neutralization Sensitivity.EBioMedicine, vol. 12, Oct. 2016, pp. 196–207. Pubmed, doi:10.1016/j.ebiom.2016.08.045.
Bradley T, Trama A, Tumba N, Gray E, Lu X, Madani N, Jahanbakhsh F, Eaton A, Xia S-M, Parks R, Lloyd KE, Sutherland LL, Scearce RM, Bowman CM, Barnett S, Abdool-Karim SS, Boyd SD, Melillo B, Smith AB, Sodroski J, Kepler TB, Alam SM, Gao F, Bonsignori M, Liao H-X, Moody MA, Montefiori D, Santra S, Morris L, Haynes BF. Amino Acid Changes in the HIV-1 gp41 Membrane Proximal Region Control Virus Neutralization Sensitivity. EBioMedicine. 2016 Oct;12:196–207.
Journal cover image

Published In

EBioMedicine

DOI

EISSN

2352-3964

Publication Date

October 2016

Volume

12

Start / End Page

196 / 207

Location

Netherlands

Related Subject Headings

  • Protein Interaction Domains and Motifs
  • Neutralization Tests
  • Mutation
  • Macaca mulatta
  • Immunization
  • Humans
  • HIV-1
  • HIV Infections
  • HIV Envelope Protein gp41
  • HIV Envelope Protein gp120