Amino Acid Changes in the HIV-1 gp41 Membrane Proximal Region Control Virus Neutralization Sensitivity
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 is...
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Format: | Article |
Language: | English |
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Elsevier
2016-10-01
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Series: | EBioMedicine |
Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396416304029 |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Todd Bradley Ashley Trama Nancy Tumba Elin Gray Xiaozhi Lu Navid Madani Fatemeh Jahanbakhsh Amanda Eaton Shi-Mao Xia Robert Parks Krissey E. Lloyd Laura L. Sutherland Richard M. Scearce Cindy M. Bowman Susan Barnett Salim S. Abdool-Karim Scott D. Boyd Bruno Melillo Amos B. Smith III Joseph Sodroski Thomas B. Kepler S.Munir Alam Feng Gao Mattia Bonsignori Hua-Xin Liao M. Anthony Moody David Montefiori Sampa Santra Lynn Morris Barton F. Haynes |
spellingShingle |
Todd Bradley Ashley Trama Nancy Tumba Elin Gray Xiaozhi Lu Navid Madani Fatemeh Jahanbakhsh Amanda Eaton Shi-Mao Xia Robert Parks Krissey E. Lloyd Laura L. Sutherland Richard M. Scearce Cindy M. Bowman Susan Barnett Salim S. Abdool-Karim Scott D. Boyd Bruno Melillo Amos B. Smith III Joseph Sodroski Thomas B. Kepler S.Munir Alam Feng Gao Mattia Bonsignori Hua-Xin Liao M. Anthony Moody David Montefiori Sampa Santra Lynn Morris Barton F. Haynes Amino Acid Changes in the HIV-1 gp41 Membrane Proximal Region Control Virus Neutralization Sensitivity EBioMedicine |
author_facet |
Todd Bradley Ashley Trama Nancy Tumba Elin Gray Xiaozhi Lu Navid Madani Fatemeh Jahanbakhsh Amanda Eaton Shi-Mao Xia Robert Parks Krissey E. Lloyd Laura L. Sutherland Richard M. Scearce Cindy M. Bowman Susan Barnett Salim S. Abdool-Karim Scott D. Boyd Bruno Melillo Amos B. Smith III Joseph Sodroski Thomas B. Kepler S.Munir Alam Feng Gao Mattia Bonsignori Hua-Xin Liao M. Anthony Moody David Montefiori Sampa Santra Lynn Morris Barton F. Haynes |
author_sort |
Todd Bradley |
title |
Amino Acid Changes in the HIV-1 gp41 Membrane Proximal Region Control Virus Neutralization Sensitivity |
title_short |
Amino Acid Changes in the HIV-1 gp41 Membrane Proximal Region Control Virus Neutralization Sensitivity |
title_full |
Amino Acid Changes in the HIV-1 gp41 Membrane Proximal Region Control Virus Neutralization Sensitivity |
title_fullStr |
Amino Acid Changes in the HIV-1 gp41 Membrane Proximal Region Control Virus Neutralization Sensitivity |
title_full_unstemmed |
Amino Acid Changes in the HIV-1 gp41 Membrane Proximal Region Control Virus Neutralization Sensitivity |
title_sort |
amino acid changes in the hiv-1 gp41 membrane proximal region control virus neutralization sensitivity |
publisher |
Elsevier |
series |
EBioMedicine |
issn |
2352-3964 |
publishDate |
2016-10-01 |
description |
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. |
url |
http://www.sciencedirect.com/science/article/pii/S2352396416304029 |
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doaj-70ba80d336514e81baec839d541fe0d32020-11-25T01:24:49ZengElsevierEBioMedicine2352-39642016-10-0112C19620710.1016/j.ebiom.2016.08.045Amino Acid Changes in the HIV-1 gp41 Membrane Proximal Region Control Virus Neutralization SensitivityTodd Bradley0Ashley Trama1Nancy Tumba2Elin Gray3Xiaozhi Lu4Navid Madani5Fatemeh Jahanbakhsh6Amanda Eaton7Shi-Mao Xia8Robert Parks9Krissey E. Lloyd10Laura L. Sutherland11Richard M. Scearce12Cindy M. Bowman13Susan Barnett14Salim S. Abdool-Karim15Scott D. Boyd16Bruno Melillo17Amos B. Smith III18Joseph Sodroski19Thomas B. Kepler20S.Munir Alam21Feng Gao22Mattia Bonsignori23Hua-Xin Liao24M. Anthony Moody25David Montefiori26Sampa Santra27Lynn Morris28Barton F. Haynes29Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USADuke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USANational Institute for Communicable Diseases, Johannesburg 2131, South AfricaNational Institute for Communicable Diseases, Johannesburg 2131, South AfricaDuke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USADana-Farber Cancer Institute, Boston, MA 02215, USADana-Farber Cancer Institute, Boston, MA 02215, USADuke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USADuke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USADuke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USADuke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USADuke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USADuke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USADuke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USANovartis Vaccines and Diagnostics, Inc., Cambridge, MA, USACenter for AIDS Program of Research in South Africa, University of KwaZulu-Natal, Durban 4013, South AfricaStanford University, Palo Alto, CA 94305, USAUniversity of Pennsylvania, Philadelphia, PA 19104, USAUniversity of Pennsylvania, Philadelphia, PA 19104, USADana-Farber Cancer Institute, Boston, MA 02215, USABoston University, Boston, MA 02118, USADuke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USADuke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USADuke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USADuke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USADuke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USADuke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USABeth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USANational Institute for Communicable Diseases, Johannesburg 2131, South AfricaDuke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USAMost 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.http://www.sciencedirect.com/science/article/pii/S2352396416304029 |