title: Effect of mutations in the V3 loop of HIV-1 gp120 on infectivity and susceptibility to proteolytic cleavage.
abstract: It has been suggested that the V3 domain of human immunodeficiency virus type 1 (HIV-1) isolates has to interact with a cell-surface-associated or endosomal proteinase during virus entry into susceptible cells. To investigate this hypothesis, we examined the effect of several mutations in the V3 loop on its susceptibility to proteolytic cleavage by thrombin and cathepsin E and compared it with the effect of these mutations on viral infectivity. The data obtained indicate that, if an interaction between the V3 loop and a proteinase is indeed crucial for viral entry, the substrate requirements for such a proteinase(s) would have to be very complex. In particular, it seems unlikely that a single enzyme with a unique specificity would be able to interact with all of the different HIV-1 and HIV-2/SIV strains isolated so far. Therefore, one would have to postulate the involvement of several cellular proteinases, or proteases with multiple specificities, in V3-based viral tropism.
authors.affiliation: Chester Beatty Laboratories, Institute of Cancer Research, London, UK.
authors.forename: T F
authors.initials: TF
authors.lastname: Schulz
authors.forename: J D
authors.initials: JD
authors.lastname: Reeves
authors.forename: J G
authors.initials: JG
authors.lastname: Hoad
authors.forename: C
authors.initials: C
authors.lastname: Tailor
authors.forename: P
authors.initials: P
authors.lastname: Stephens
authors.forename: G
authors.initials: G
authors.lastname: Clements
authors.forename: S
authors.initials: S
authors.lastname: Ortlepp
authors.forename: K A
authors.initials: KA
authors.lastname: Page
authors.forename: J P
authors.initials: JP
authors.lastname: Moore
authors.forename: R A
authors.initials: RA
authors.lastname: Weiss
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D020059:Cathepsin E; D002403:Cathepsins / Q000378:metabolism; D002460:Cell Line; D015699:HIV Envelope Protein gp120 / Q000235:genetics* / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D013917:Thrombin / Q000378:metabolism
chemical_list: D015699:HIV Envelope Protein gp120; D002403:Cathepsins; D013917:Thrombin; D020059:Cathepsin E