CD4 downregulation precedes Env expression and protects HIV-1-infected cells from ADCC mediated by non-neutralizing antibodies.

A32 ADCC Env HIV-1 RNA-flow fish bNAbs hu-mice nnAbs

Journal

mBio
ISSN: 2150-7511
Titre abrégé: mBio
Pays: United States
ID NLM: 101519231

Informations de publication

Date de publication:
07 Oct 2024
Historique:
medline: 7 10 2024
pubmed: 7 10 2024
entrez: 7 10 2024
Statut: aheadofprint

Résumé

HIV-1 envelope glycoprotein (Env) conformation substantially impacts antibody-dependent cellular cytotoxicity (ADCC). Envs from primary HIV-1 isolates adopt a prefusion "closed" conformation, which is targeted by broadly neutralizing antibodies (bnAbs). CD4 binding drives Env into more "open" conformations, which are recognized by non-neutralizing Abs (nnAbs). To better understand Env-Ab and Env-CD4 interaction in CD4+ T cells infected with HIV-1, we simultaneously measured antibody binding and HIV-1 mRNA expression using multiparametric flow cytometry and RNA flow fluorescent Antibody-dependent cellular cytotoxicity (ADCC) represents an effective immune response for clearing virally infected cells, making ADCC-mediating antibodies promising therapeutic candidates for HIV-1 cure strategies. Broadly neutralizing antibodies (bNAbs) target epitopes present on the native "closed" envelope glycoprotein (Env), while non-neutralizing antibodies (nnAbs) recognize epitopes exposed upon Env-CD4 interaction. Here, we provide evidence that

Identifiants

pubmed: 39373535
doi: 10.1128/mbio.01827-24
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

e0182724

Auteurs

Jonathan Richard (J)

Centre de Recherche du CHUM, Montréal, Québec, Canada.
Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montréal, Québec, Canada.

Gérémy Sannier (G)

Centre de Recherche du CHUM, Montréal, Québec, Canada.
Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montréal, Québec, Canada.

Li Zhu (L)

Department of Internal Medicine, Section of Infectious Diseases, Yale University School of Medicine, New Haven, Connecticut, USA.

Jérémie Prévost (J)

Centre de Recherche du CHUM, Montréal, Québec, Canada.
Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montréal, Québec, Canada.

Lorie Marchitto (L)

Centre de Recherche du CHUM, Montréal, Québec, Canada.
Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montréal, Québec, Canada.

Mehdi Benlarbi (M)

Centre de Recherche du CHUM, Montréal, Québec, Canada.
Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montréal, Québec, Canada.

Guillaume Beaudoin-Bussières (G)

Centre de Recherche du CHUM, Montréal, Québec, Canada.
Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montréal, Québec, Canada.

Hongil Kim (H)

Department of Internal Medicine, Section of Infectious Diseases, Yale University School of Medicine, New Haven, Connecticut, USA.

Yaping Sun (Y)

Department of Internal Medicine, Section of Infectious Diseases, Yale University School of Medicine, New Haven, Connecticut, USA.

Debashree Chatterjee (D)

Centre de Recherche du CHUM, Montréal, Québec, Canada.

Halima Medjahed (H)

Centre de Recherche du CHUM, Montréal, Québec, Canada.

Catherine Bourassa (C)

Centre de Recherche du CHUM, Montréal, Québec, Canada.

Gloria-Gabrielle Delgado (G-G)

Centre de Recherche du CHUM, Montréal, Québec, Canada.

Mathieu Dubé (M)

Centre de Recherche du CHUM, Montréal, Québec, Canada.

Frank Kirchhoff (F)

Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany.

Beatrice H Hahn (BH)

Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Priti Kumar (P)

Department of Internal Medicine, Section of Infectious Diseases, Yale University School of Medicine, New Haven, Connecticut, USA.

Daniel E Kaufmann (DE)

Department of Medicine, Université de Montréal, Montreal, Quebec, Canada.
Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, California, USA.
Division of Infectious Diseases, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.

Andrés Finzi (A)

Centre de Recherche du CHUM, Montréal, Québec, Canada.
Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montréal, Québec, Canada.

Classifications MeSH