title: Adhesion and fusion efficiencies of human immunodeficiency virus type 1 (HIV-1) surface proteins.
abstract: In about half of patients infected with HIV-1 subtype B, viral populations shift from utilizing the transmembrane protein CCR5 to CXCR4, as well as or instead of CCR5, during late stage progression of the disease. How the relative adhesion efficiency and fusion competency of the viral Env proteins relate to infection during this transition is not well understood. Using a virus-cell fusion assay and live-cell single-molecule force spectroscopy, we compare the entry competency of viral clones to tensile strengths of the individual Env-receptor bonds of Env proteins obtained from a HIV-1 infected patient prior to and during coreceptor switching. The results suggest that the genetic determinants of viral entry were predominantly enriched in the C3, HR1 and CD regions rather than V3. Env proteins can better mediate entry into cells after coreceptor switch; this effective entry capacity does not correlate with the bond strengths between viral Env and cellular receptors.
authors.affiliation: 1] Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, 3400 North Charles Street, Baltimore, Maryland 21218, USA [2].
authors.forename: Terrence M
authors.initials: TM
authors.lastname: Dobrowsky
authors.forename: S Alireza
authors.initials: SA
authors.lastname: Rabi
authors.forename: Rebecca
authors.initials: R
authors.lastname: Nedellec
authors.forename: Brian R
authors.initials: BR
authors.lastname: Daniels
authors.forename: James I
authors.initials: JI
authors.lastname: Mullins
authors.forename: Donald E
authors.initials: DE
authors.lastname: Mosier
authors.forename: Robert F
authors.initials: RF
authors.lastname: Siliciano
authors.forename: Denis
authors.initials: D
authors.lastname: Wirtz
mesh_terms: D015704:CD4 Antigens / Q000378:metabolism; D002460:Cell Line; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D019713:Receptors, CCR5 / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism; D015728:Receptors, HIV / Q000378:metabolism; D053585:Virus Attachment; D053586:Virus Internalization; D054299:env Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D015704:CD4 Antigens; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D015728:Receptors, HIV; D054299:env Gene Products, Human Immunodeficiency Virus