• 作者：Todd Bradley^a ; ¹ ; ^{todd.bradley@duke.edu" class="auth_mail" title="E-mail the corresponding author} ; Ashley Trama^a ; ¹ ; Nancy Tumba^b ; Elin Gray^b ; Xiaozhi Lu^a ; Navid Madani^c ; ^d ; Fatemeh Jahanbakhsh^c ; Amanda Eaton^a ; Shi-Mao Xia^a ; Robert Parks^a ; Krissey E. Lloyd^a ; Laura L. Sutherland^a ; Richard M. Scearce^a ; Cindy M. Bowman^a ; Susan Barnett^e ; Salim S. Abdool-Karim^f ; ^g ; Scott D. Boyd^h ; Bruno Melilloⁱ ; Amos B. Smith IIIⁱ ; Joseph Sodroski^c ; ^d ; Thomas B. Kepler^j ; S.Munir Alam^a ; Feng Gao^a ; Mattia Bonsignori^a ; Hua-Xin Liao^a ; M. Anthony Moody^a ; David Montefiori^a ; Sampa Santra^k ; Lynn Morris^b ; ^f ; ^l ; Barton F. Haynes^a ; ^{barton.haynes@duke.edu" class="auth_mail" title="E-mail the corresponding author}
• 刊名：EBioMedicine
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：12
• 期：Complete
• 页码：196-207
• 全文大小：747 K

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Amino acid changes in the HIV gp41 MPER can regulate neutralization sensitivity of distal epitopes.

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MPER antibodies isolated early are resistant to MPER changes that enhance neutralization sensitivity.

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HIV gp41 MPER is critical for determining overall HIV envelope conformations.

The HIV-1 envelope protein (Env) is the primary target for neutralizing antibodies. Most HIV-1 vaccines elicit neutralizing antibodies that are active against highly neutralization-sensitive (tier-1) or rare vaccine-matched more neutralization-resistant (tier-2) viruses, but no vaccine has induced antibodies that can broadly neutralize heterologous tier-2 viruses. In this study, we identified changes that occurred in two HIV-1-infected individuals in the membrane proximal region of the HIV-1 Env that resulted in neutralization sensitivity to antibodies targeting distal epitopes on the HIV Env. These single-residue changes thus transformed tier-2 viruses into tier-1 viruses, highlighting the importance of MPER residues in maintaining neutralization-resistant virus.