title: Mechanistic studies of a T20-dependent human immunodeficiency virus type 1 variant.
abstract: We previously described a T20-dependent human immunodeficiency virus type 1 variant from a patient on T20 therapy. This virus carries two mutations in the gp41 domain of the envelope protein (Env) that was proposed to undergo a premature conformational switch to the 6-helix bundle structure. The T20 peptide can rescue this hyperfusogenic Env protein by preventing the premature switch and preserving an earlier prefusion conformation, thus restoring virus infectivity and replication. In this study, we set out to critically test this mechanistic explanation with alternative effectors that may control the Env switch, including other fusion inhibitors and antibodies that target gp41.
authors.affiliation: Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam, Academic Medical Center of the University of Amsterdam, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands.
authors.forename: Chris
authors.initials: C
authors.lastname: Baldwin
authors.forename: Ben
authors.initials: B
authors.lastname: Berkhout
mesh_terms: D002460:Cell Line; D000077560:Enfuvirtide; D016655:HIV Core Protein p24 / Q000096:biosynthesis; D015700:HIV Envelope Protein gp41 / Q000235:genetics* / Q000378:metabolism*; D023581:HIV Fusion Inhibitors / Q000378:metabolism*; D015497:HIV-1 / Q000235:genetics* / Q000502:physiology*; D006801:Humans; D008954:Models, Biological; D008958:Models, Molecular; D020125:Mutation, Missense; D010446:Peptide Fragments / Q000378:metabolism*; D053586:Virus Internalization; D014779:Virus Replication
chemical_list: D016655:HIV Core Protein p24; D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors; D010446:Peptide Fragments; D000077560:Enfuvirtide