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

被引：31

作者：

Bradley, Todd ^{[1
]}

Trama, Ashley ^{[1
]}

Tumba, Nancy ^{[2
]}

Gray, Elin ^{[2
]}

Lu, Xiaozhi ^{[1
]}

Madani, Navid ^{[3
,4
]}

Jahanbakhsh, Fatemeh ^{[3
]}

Eaton, Amanda ^{[1
]}

Xia, Shi-Mao ^{[1
]}

Parks, Robert ^{[1
]}

Lloyd, Krissey E. ^{[1
]}

Sutherland, Laura L. ^{[1
]}

Scearce, Richard M. ^{[1
]}

Bowman, Cindy M. ^{[1
]}

Barnett, Susan ^{[5
]}

Abdool-Karim, Salim S. ^{[6
,7
]}

Boyd, Scott D. ^{[8
]}

Melillo, Bruno ^{[9
]}

Smith, Amos B., III ^{[9
]}

Sodroski, Joseph ^{[3
,4
]}

Kepler, Thomas B. ^{[10
]}

Alam, S. Munir ^{[1
]}

Gao, Feng ^{[1
]}

Bonsignori, Mattia ^{[1
]}

Liao, Hua-Xin ^{[1
]}

Moody, M. Anthony ^{[1
]}

Montefiori, David ^{[1
]}

Santra, Sampa ^{[11
]}

Morris, Lynn ^{[2
,6
,12
]}

Haynes, Barton F. ^{[1
]}

机构：

[1] Duke Univ, Med Ctr, Duke Human Vaccine Inst, Durham, NC 27710 USA

[2] Natl Inst Communicable Dis, ZA-2131 Johannesburg, South Africa

[3] Dana Farber Canc Inst, Boston, MA 02215 USA

[4] Harvard Med Sch, Boston, MA 02115 USA

[5] Novartis Vaccines & Diagnost Inc, Cambridge, MA USA

[6] Univ KwaZulu Natal, Ctr AIDS Program Res South Africa, ZA-4013 Durban, South Africa

[7] Columbia Univ, New York, NY 10032 USA

[8] Stanford Univ, Palo Alto, CA 94305 USA

[9] Univ Penn, Philadelphia, PA 19104 USA

[10] Boston Univ, Boston, MA 02118 USA

[11] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA

[12] Univ Witwatersrand, Fac Hlth Sci, ZA-2131 Johannesburg, South Africa

来源：

EBIOMEDICINE | 2016年 / 12卷

关键词：

EXTERNAL REGION; MONOCLONAL-ANTIBODIES; TYPE-1; GP41; ENVELOPE GLYCOPROTEINS; IMMUNE PRESSURE; CELL RESPONSES; BINDING; EPITOPE; SITE; IDENTIFICATION;

D O I：

10.1016/j.ebiom.2016.08.045

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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. (C) 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

引用

页码：196 / 207

页数：12

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