Three families of CD4-induced antibodies are associated with the capacity of plasma from people living with HIV to mediate ADCC in the presence of CD4-mimetics.

Autor:	Tauzin A; Centre de Recherche du CHUM, Montreal, Quebec, Canada.; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, Quebec, Canada., Marchitto L; Centre de Recherche du CHUM, Montreal, Quebec, Canada.; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, Quebec, Canada., Bélanger É; Centre de Recherche du CHUM, Montreal, Quebec, Canada.; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, Quebec, Canada., Benlarbi M; Centre de Recherche du CHUM, Montreal, Quebec, Canada.; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, Quebec, Canada., Beaudoin-Bussières G; Centre de Recherche du CHUM, Montreal, Quebec, Canada.; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, Quebec, Canada., Prévost J; Centre de Recherche du CHUM, Montreal, Quebec, Canada.; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, Quebec, Canada., Yang D; Department of Chemistry, School of Arts and Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Chiu T-J; Department of Chemistry, School of Arts and Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Chen H-C; Department of Chemistry, School of Arts and Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Bourassa C; Centre de Recherche du CHUM, Montreal, Quebec, Canada., Medjahed H; Centre de Recherche du CHUM, Montreal, Quebec, Canada., Korzeniowski MK; Infectious Diseases Division, Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA., Gottumukkala S; Infectious Diseases Division, Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA., Tolbert WD; Infectious Diseases Division, Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA., Richard J; Centre de Recherche du CHUM, Montreal, Quebec, Canada.; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, Quebec, Canada., Smith AB 3rd; Department of Chemistry, School of Arts and Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Pazgier M; Infectious Diseases Division, Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA., Finzi A; Centre de Recherche du CHUM, Montreal, Quebec, Canada.; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, Quebec, Canada.
Jazyk:	angličtina
Zdroj:	Journal of virology [J Virol] 2024 Oct 22; Vol. 98 (10), pp. e0096024. Date of Electronic Publication: 2024 Sep 04.
DOI:	10.1128/jvi.00960-24
Abstrakt:	CD4-mimetics (CD4mcs) are small molecule compounds that mimic the interaction of the CD4 receptor with HIV-1 envelope glycoproteins (Env). Env from primary viruses normally samples a "closed" conformation that occludes epitopes recognized by CD4-induced (CD4i) non-neutralizing antibodies (nnAbs). CD4mcs induce conformational changes on Env resulting in the exposure of these otherwise inaccessible epitopes. Here, we evaluated the capacity of plasma from a cohort of 50 people living with HIV to recognize HIV-1-infected cells and eliminate them by antibody-dependent cellular cytotoxicity (ADCC) in the presence of a potent indoline CD4mc. We observed a marked heterogeneity among plasma samples. By measuring the levels of different families of CD4i Abs, we found that the levels of anti-cluster A, anti-coreceptor binding site, and anti-gp41 cluster I antibodies are responsible for plasma-mediated ADCC in the presence of CD4mc. Importance: There are several reasons that make it difficult to target the HIV reservoir. One of them is the capacity of infected cells to prevent the recognition of HIV-1 envelope glycoproteins (Env) by commonly elicited antibodies in people living with HIV. Small CD4-mimetic compounds expose otherwise occluded Env epitopes, thus enabling their recognition by non-neutralizing antibodies (nnAbs). A better understanding of the contribution of these antibodies to eliminate infected cells in the presence of CD4mc could lead to the development of therapeutic cure strategies. Competing Interests: The authors declare no conflict of interest.
Databáze:	MEDLINE
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