title: The pH dependence of HIV-1 capsid assembly and its interaction with cyclophilin A.
abstract: Immature HIV-1 virions have spherical cores which become conical due to cleavage of the capsid domain of Gag. Here, we have used an immature form of capsid and show by electron microscopy, atomic force microscopy and single angle light scattering that it aggregates to spherical cores resembling immature virions at high ionic strengths and at pH values above 6. Dynamic angle light scattering of the dissociated protein shows structural changes that promote oligomerization above pH 6. We then examined the role of the required host protein cyclophilin A on assembly. Cyclophilin A is incorporated into virions at a 1:10 cyclophilin A/capsid ratio. We find that although cyclophilin A does not affect the oligomerization rate or stability of immature capsid cores, it does bind strongly to immature capsid at physiological stoichiometry above pH 6. This association serves as an entry route of cyclophilin A into HIV-1 virions.
authors.affiliation: Department of Physiology and Biophysics, State University of New York at Stony Brook, Stony Brook, NY 11794, USA.
authors.forename: Marjorie
authors.initials: M
authors.lastname: Bon Homme
authors.forename: Stanislaus
authors.initials: S
authors.lastname: Wong
authors.forename: Carol
authors.initials: C
authors.lastname: Carter
authors.forename: Suzanne
authors.initials: S
authors.lastname: Scarlata
mesh_terms: D002213:Capsid / Q000737:chemistry* / Q000378:metabolism; D021984:Cyclophilin A / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism; D015497:HIV-1 / Q000737:chemistry* / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008027:Light; D018625:Microscopy, Atomic Force; D008854:Microscopy, Electron; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012542:Scattering, Radiation; D013050:Spectrometry, Fluorescence
chemical_list: D011994:Recombinant Proteins; D021984:Cyclophilin A