CD4 mimetics sensitize HIV-1-infected cells to ADCC.

TitleCD4 mimetics sensitize HIV-1-infected cells to ADCC.
Publication TypeJournal Article
Year of Publication2015
AuthorsRichard J, Veillette M, Brassard N, Iyer SS, Roger M, Martin L, Pazgier M, Schön A, Freire E, Routy J-P, Smith AB, Park J, Jones DM, Courter JR, Melillo BN, Kaufmann DE, Hahn BH, Permar SR, Haynes BF, Madani N, Sodroski JG, Finzi A
JournalProc Natl Acad Sci U S A
Volume112
Issue20
PaginationE2687-94
Date Published05/19/2015
ISSN1091-6490
Abstract

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.

DOI10.1073/pnas.1506755112
Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID25941367
Grant ListUM1 AI100663 / AI / NIAID NIH HHS / United States
CHAVI-ID: 
1
Cover Picture: