CD4 mimetics sensitize HIV-1-infected cells to ADCC.
Proc Natl Acad Sci U S A
; 112(20): E2687-94, 2015 May 19.
Article
en En
| MEDLINE
| ID: mdl-25941367
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.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Antígenos CD4
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Infecciones por VIH
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VIH-1
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Citotoxicidad Celular Dependiente de Anticuerpos
Límite:
Humans
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Año:
2015
Tipo del documento:
Article