2024
Epistatic pathways can drive HIV-1 escape from integrase strand transfer inhibitors
Hikichi Y, Grover J, Schäfer A, Mothes W, Freed E. Epistatic pathways can drive HIV-1 escape from integrase strand transfer inhibitors. Science Advances 2024, 10: eadn0042. PMID: 38427738, PMCID: PMC10906922, DOI: 10.1126/sciadv.adn0042.Peer-Reviewed Original ResearchConceptsIntegrase strand transfer inhibitorsClasses of antiretroviralsHuman immunodeficiency virusStrand transfer inhibitorsHIV-1Env mutationsTransfer inhibitorsIntegrase strand transfer inhibitor dolutegravirHIV-1 escapeResistance to dolutegravirResistance to antiretroviralsAbsence of resistance mutationsClasses of drugsCell-cell transferVirological failureImmunodeficiency virusResistance mutationsGene mutationsEnvelope glycoproteinAntiretroviralsEnvResistance mechanismsDolutegravirMutationsIntegrase
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
2000
Retroviral Entry Mediated by Receptor Priming and Low pH Triggering of an Envelope Glycoprotein
Mothes W, Boerger A, Narayan S, Cunningham J, Young J. Retroviral Entry Mediated by Receptor Priming and Low pH Triggering of an Envelope Glycoprotein. Cell 2000, 103: 679-689. PMID: 11106737, DOI: 10.1016/s0092-8674(00)00170-7.Peer-Reviewed Original Research