2024
Design of soluble HIV-1 envelope trimers free of covalent gp120-gp41 bonds with prevalent native-like conformation
Zhang P, Gorman J, Tsybovsky Y, Lu M, Liu Q, Gopan V, Singh M, Lin Y, Miao H, Seo Y, Kwon A, Olia A, Chuang G, Geng H, Lai Y, Zhou T, Mascola J, Mothes W, Kwong P, Lusso P. Design of soluble HIV-1 envelope trimers free of covalent gp120-gp41 bonds with prevalent native-like conformation. Cell Reports 2024, 43: 114518. PMID: 39028623, PMCID: PMC11459465, DOI: 10.1016/j.celrep.2024.114518.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, NeutralizingCD4 AntigensHIV Envelope Protein gp120HIV Envelope Protein gp41HIV-1HumansProtein BindingProtein ConformationProtein MultimerizationSolubility
2023
HIV-1 Env trimers asymmetrically engage CD4 receptors in membranes
Li W, Qin Z, Nand E, Grunst M, Grover J, Bess J, Lifson J, Zwick M, Tagare H, Uchil P, Mothes W. HIV-1 Env trimers asymmetrically engage CD4 receptors in membranes. Nature 2023, 623: 1026-1033. PMID: 37993716, PMCID: PMC10686830, DOI: 10.1038/s41586-023-06762-6.Peer-Reviewed Original ResearchConceptsHIV-1 Env trimersCD4 moleculeHuman immunodeficiency virus-1 (HIV-1) infectionEnv trimersAntibody-mediated immune responsesEnv-CD4 interactionVirus-1 infectionVaccine immunogen designViral envelope glycoproteinsHIV-1Immune responseCD4 receptorImmunogen designEnvelope glycoproteinVirus-like particlesCD4EnvHost cell membraneTemsavir blocks the immunomodulatory activities of HIV-1 soluble gp120
Richard J, Prévost J, Bourassa C, Brassard N, Boutin M, Benlarbi M, Goyette G, Medjahed H, Gendron-Lepage G, Gaudette F, Chen H, Tolbert W, Smith A, Pazgier M, Dubé M, Clark A, Mothes W, Kaufmann D, Finzi A. Temsavir blocks the immunomodulatory activities of HIV-1 soluble gp120. Cell Chemical Biology 2023, 30: 540-552.e6. PMID: 36958337, PMCID: PMC10198848, DOI: 10.1016/j.chembiol.2023.03.003.Peer-Reviewed Original ResearchConceptsAntibody-dependent cellular cytotoxicityUninfected bystander CD4Gp120-CD4 interactionCytokine burstBystander CD4Immunomodulatory activityMultiple immune cellsHIV-1 attachment inhibitorsOverall antigenicityADCC responsesClinical benefitSoluble gp120Immune cellsCellular cytotoxicityAttachment inhibitorsCD4 interactionGp120 bindsCD4Gp120Viral entryEnvelope glycoproteinCD4 downregulationTemsavirCellsAntigenicity
2018
HIV-1 Env trimer opens through an asymmetric intermediate in which individual protomers adopt distinct conformations
Ma X, Lu M, Gorman J, Terry DS, Hong X, Zhou Z, Zhao H, Altman RB, Arthos J, Blanchard SC, Kwong PD, Munro JB, Mothes W. HIV-1 Env trimer opens through an asymmetric intermediate in which individual protomers adopt distinct conformations. ELife 2018, 7: e34271. PMID: 29561264, PMCID: PMC5896952, DOI: 10.7554/elife.34271.Peer-Reviewed Original Research
2014
Conformational dynamics of single HIV-1 envelope trimers on the surface of native virions
Munro JB, Gorman J, Ma X, Zhou Z, Arthos J, Burton DR, Koff WC, Courter JR, Smith AB, Kwong PD, Blanchard SC, Mothes W. Conformational dynamics of single HIV-1 envelope trimers on the surface of native virions. Science 2014, 346: 759-763. PMID: 25298114, PMCID: PMC4304640, DOI: 10.1126/science.1254426.Peer-Reviewed Original Research