2024
CD4 downregulation precedes Env expression and protects HIV-1-infected cells from ADCC mediated by non-neutralizing antibodies.
Richard J, Sannier G, Zhu L, Prévost J, Marchitto L, Benlarbi M, Beaudoin-Bussières G, Kim H, Sun Y, Chatterjee D, Medjahed H, Bourassa C, Delgado G, Dubé M, Kirchhoff F, Hahn B, Kumar P, Kaufmann D, Finzi A. CD4 downregulation precedes Env expression and protects HIV-1-infected cells from ADCC mediated by non-neutralizing antibodies. MBio 2024, e0182724. PMID: 39373535, DOI: 10.1128/mbio.01827-24.Peer-Reviewed Original ResearchAntibody-dependent cellular cytotoxicityProductively infected cellsEnv-CD4 interactionNon-neutralizing antibodiesHIV-1CD4 downmodulationEnv expressionCellular cytotoxicityResistance to antibody-dependent cellular cytotoxicityHIV-1-infected humanized miceInfected cellsHIV-1 cure strategiesHIV-1 mRNA expressionHIV-1-infected cellsCD4+ T cellsHIV-1 envelope glycoproteinMRNA expressionADCC-mediating antibodiesNon-neutralizing AbsCell surface CD4HIV-1 isolatesImmunotherapy-based strategiesMultiparametric flow cytometryVirally infected cellsEffective immune response
2022
HIV-1 Vpu restricts Fc-mediated effector functions in vivo
Prévost J, Anand S, Rajashekar J, Zhu L, Richard J, Goyette G, Medjahed H, Gendron-Lepage G, Chen H, Chen Y, Horwitz J, Grunst M, Zolla-Pazner S, Haynes B, Burton D, Flavell R, Kirchhoff F, Hahn B, Smith A, Pazgier M, Nussenzweig M, Kumar P, Finzi A. HIV-1 Vpu restricts Fc-mediated effector functions in vivo. Cell Reports 2022, 41: 111624. PMID: 36351384, PMCID: PMC9703018, DOI: 10.1016/j.celrep.2022.111624.Peer-Reviewed Original ResearchConceptsAntibody-dependent cellular cytotoxicityEffector functionsFc-mediated effector functionsHIV-1-infected cellsWild-type virusCorrelates of protectionRV144 vaccine trialHIV-1 infectionNon-neutralizing antibodiesFc effector functionsCell surface CD4Viral envelope glycoproteinsViral loadHumanized miceHumoral responseVaccine trialsCellular cytotoxicityHIV-1 VpuVpu expressionEnvelope glycoproteinInfected cellsNnAbsVirusVpuAdministrationA Fc-enhanced NTD-binding non-neutralizing antibody delays virus spread and synergizes with a nAb to protect mice from lethal SARS-CoV-2 infection
Beaudoin-Bussières G, Chen Y, Ullah I, Prévost J, Tolbert WD, Symmes K, Ding S, Benlarbi M, Gong SY, Tauzin A, Gasser R, Chatterjee D, Vézina D, Goyette G, Richard J, Zhou F, Stamatatos L, McGuire AT, Charest H, Roger M, Pozharski E, Kumar P, Mothes W, Uchil PD, Pazgier M, Finzi A. A Fc-enhanced NTD-binding non-neutralizing antibody delays virus spread and synergizes with a nAb to protect mice from lethal SARS-CoV-2 infection. Cell Reports 2022, 38: 110368. PMID: 35123652, PMCID: PMC8786652, DOI: 10.1016/j.celrep.2022.110368.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, NeutralizingAntibodies, ViralAntibody-Dependent Cell CytotoxicityCOVID-19COVID-19 SerotherapyDisease Models, AnimalEpitopesHumansImmunization, PassiveImmunoglobulin Fab FragmentsImmunoglobulin Fc FragmentsMiceProtein BindingProtein ConformationSARS-CoV-2Spike Glycoprotein, Coronavirus