HIV Nef and Vpu protect HIV-infected CD4+ T cells from antibody-mediated cell lysis through down-modulation of CD4 and BST2

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作者：Tram NQ Pham (1) Sabelo Lukhele (1) Fadi Hajjar (1) Jean-Pierre Routy (2) éric A Cohen (1) (3)
关键词：HIV accessory proteins Nef and Vpu ; BST2 ; CD4 ; Env interactions ; ADCC
刊名：Retrovirology
出版年：2014
出版时间：December 2014
年：2014
卷：11
期：1
全文大小：1,180 KB
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作者单位：Tram NQ Pham (1) Sabelo Lukhele (1) Fadi Hajjar (1) Jean-Pierre Routy (2) éric A Cohen (1) (3) 1. Laboratory of Human Retrovirology, Institut de Recherches Cliniques de Montréal (IRCM), 110 Pine Avenue West, Montreal, H2W 1R7, Quebec, Canada 2. Division of Hematology and Chronic Viral Illness Service, Royal Victoria Hospital, McGill University Health Centre, Montreal, H3A 1A1, Quebec, Canada 3. Department of Microbiology, Infectiology and Immunology, Université de Montréal, Montréal, H3T 1J4, Québec, Canada
ISSN：1742-4690

文摘

Background HIV proteins Nef and Vpu down-modulate various host factors to evade immune defenses. Indeed, the CD4 receptor is down-regulated by Nef and Vpu, whereas virion-tethering BST2 is depleted by Vpu. Antibody-dependent cell-mediated cytotoxicity (ADCC) is increasingly recognized as a potentially powerful anti-HIV response. Given that epitopes which are specific for ADCC-competent anti-HIV antibodies are transitionally exposed upon CD4-mediated HIV entry, we investigated whether by depleting CD4 and BST2, HIV could negatively affect ADCC function. Results Using anti-envelope (Env) Abs A32 and 2G12 to trigger ADCC activity, we find that interactions between CD4 and Env within infected cells expose ADCC-targeted epitopes on cell-surface Env molecules, marking infected T cells for lysis by immune cells. We also provide evidence to show that by cross-linking nascent virions at the plasma membrane, hence increasing cell-surface Env density, BST2 further enhances the efficiency of this antiviral process. The heightened susceptibility of T cells infected with a virus lacking Nef and Vpu to ADCC was recapitulated when plasmas from HIV-infected patients were used as an alternative source of Abs. Conclusions Our data unveil a mechanism by which HIV Nef and Vpu function synergistically to protect infected cells from ADCC and promote viral persistence. These findings also renew the potential practical relevance of ADCC function in vivo.

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