• 作者：Jonathan Richard^a ; ^b ; ^{jonathan.richard.1@umontreal.ca" class="auth_mail" title="E-mail the corresponding author} ; Beatriz Pacheco^a ; Neelakshi Gohain^c ; Maxime Veillette^a ; ^b ; Shilei Ding^a ; ^b ; Nirmin Alsahafi^a ; ^d ; William D. Tolbert^c ; Jé ; ré ; mie Pré ; vost^a ; ^b ; Jean-Philippe Chapleau^a ; ^b ; Mathieu Coutu^a ; Manxue Jia^e ; Nathalie Brassard^a ; Jongwoo Park^f ; Joel R. Courter^f ; Bruno Melillo^f ; Loï ; c Martin^g ; Cé ; cile Tremblay^a ; ^b ; Beatrice H. Hahn^h ; ⁱ ; Daniel E. Kaufmann^a ; ^j ; ^k ; ^l ; Xueling Wu^e ; Amos B. Smith III^f ; Joseph Sodroski^m ; ⁿ ; Marzena Pazgier^c ; André ; s Finzi^a ; ^b ; ^d ; ^{andres.finzi@umontreal.ca" class="auth_mail" title="E-mail the corresponding author}
• 关键词：HIV-1 ; Envelope glycoproteins ; CD4 ; Non-neutralizing antibodies ; ADCC ; CD4-mimetics
• 刊名：EBioMedicine
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：12
• 期：Complete
• 页码：208-218
• 全文大小：727 K

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CD4-mimetics fail to enhance recognition of infected cells by anti-cluster A antibodies (Abs).

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Co-receptor binding site Abs in conjunction with CD4-mimetics allow binding of Env by anti-cluster A Abs.

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Co-receptor binding site Abs help CD4-mimetics sensitize HIV-1-infected cells to ADCC.

HIV-1 developed sophisticated strategies to conceal vulnerable epitopes of its envelope glycoproteins (Env) recognized by antibody-dependent cellular cytotoxicity (ADCC)-mediating antibodies. CD4-mimetics (CD4mc) were shown to sensitize HIV-1-infected cells to ADCC induced by HIV + sera. Here we show that this response requires a sequential opening of Env at the surface of HIV-1-infected cells. Co-receptor binding site antibodies, also present in HIV + sera, are required to expose ADCC-mediating epitopes recognized by anti-cluster A antibodies upon CD4mc addition. The understanding of the conformational changes required to expose anti-cluster A epitopes might be important in the design of new strategies aimed at fighting HIV-1.