|Title||CD4 mimetics sensitize HIV-1-infected cells to ADCC.|
|Publication Type||Journal Article|
|Year of Publication||2015|
|Authors||Richard 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|
|Journal||Proc Natl Acad Sci U S A|
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.
|Alternate Journal||Proc. Natl. Acad. Sci. U.S.A.|
|Grant List||UM1 AI100663 / AI / NIAID NIH HHS / United States|
CD4 mimetics sensitize HIV-1-infected cells to ADCC.