CD4 mimetics sensitize HIV-1-infected cells to ADCC.
Journal Article (Journal Article)
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.
Full Text
Duke Authors
Cited 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
Published Date
- May 19, 2015
Published In
Volume / Issue
- 112 / 20
Start / End Page
- E2687 - E2694
PubMed ID
- 25941367
Pubmed Central ID
- PMC4443331
Electronic International Standard Serial Number (EISSN)
- 1091-6490
Digital Object Identifier (DOI)
- 10.1073/pnas.1506755112
Language
- eng
Conference Location
- United States