CD4 mimetics sensitize HIV-1-infected cells to ADCC

Richard Jonathan; Veillette Maxime; Brassard NathalieIyerc Shilpa S.Roger MichelMartin LoicPazgier MarzenaSchoen ArneFreire ErnestoRouty Jean-PierreSmith Amos B. IIIPark JongwooJones David M.Courter Joel R.Melillo Bruno N.Kaufmann Daniel E.Hahn Beatrice H.Permar Sallie R.Haynes Barton F.Madani NavidSodroski Joseph G.Finzi Andres

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CD4 mimetics sensitize HIV-1-infected cells to ADCC

机译：CD4 mimetics sensitize HIV-1-infected cells to ADCC

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HIV-1-infected cells presenting envelope glycoproteins (Env) in the CD4-bound conformation on their surface are preferentially targeted by antibody-dependent cell-mediated cytotoxicity (ADCC). HIV-1 has evolved a sophisticated mechanism to avoid exposure of ADCC-mediating Env epitopes by down-regulating CD4 and by limiting the overall amount of Env at the cell surface. Here we report that small-molecule CD4-mimetic compounds induce the CD4-bound conformation of Env, and thereby sensitize cells infected with primary HIV-1 isolates to ADCC mediated by antibodies present in sera, cervicovaginal lavages, and breast milk from HIV-1-infected individuals. Importantly, we identified one CD4 mimetic with the capacity to sensitize endogenously infected ex vivo-amplified primary CD4 T cells to ADCC killing mediated by autologous sera and effector cells. Thus, CD4 mimetics hold the promise of therapeutic utility in preventing and controlling HIV-1 infection.

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《Proceedings of the National Academy of Sciences of the United States of America》 |2015年第20期|E2687-E2694|共8页
作者
Richard Jonathan; Veillette Maxime; Brassard NathalieIyerc Shilpa S.Roger MichelMartin LoicPazgier MarzenaSchoen ArneFreire ErnestoRouty Jean-PierreSmith Amos B. IIIPark JongwooJones David M.Courter Joel R.Melillo Bruno N.Kaufmann Daniel E.Hahn Beatrice H.Permar Sallie R.Haynes Barton F.Madani NavidSodroski Joseph G.Finzi Andres;
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作者单位

Univ Penn, Sch Arts & Sci, Dept Chem, Philadelphia, PA 19104 USA;

Univ Montreal, Ctr Hosp, Ctr Rech, Montreal, PQ H3C 3J7, Canada;

Harvard Univ, Massachusetts Gen Hosp, Massachusetts Inst, Ragon Inst, Cambridge, MA 02139 USAUniv Penn, Dept Med, Philadelphia, PA 19104 USADuke Univ, Med Ctr, Duke Human Vaccine Inst, Durham, NC 27710 USADana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USAInst Biol & Technol Saclay, Serv Ingn Mol Proteines, Commissariat Eergie Atom, F-91191 Gif Sur Yvette, FranceUniv Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USAJohns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USAMcGill Univ, Dept Microbiol & Immunol, Montreal, PQ H3A 2B4, Canada;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
HIV-1; envelope glycoproteins; gp120; CD4 mimetics; ADCC;

CD4 mimetics sensitize HIV-1-infected cells to ADCC

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