title: In vitro protease cleavage and computer simulations reveal the HIV-1 capsid maturation pathway.
abstract: HIV-1 virions assemble as immature particles containing Gag polyproteins that are processed by the viral protease into individual components, resulting in the formation of mature infectious particles. There are two competing models for the process of forming the mature HIV-1 core: the disassembly and de novo reassembly model and the non-diffusional displacive model. To study the maturation pathway, we simulate HIV-1 maturation in vitro by digesting immature particles and assembled virus-like particles with recombinant HIV-1 protease and monitor the process with biochemical assays and cryoEM structural analysis in parallel. Processing of Gag in vitro is accurate and efficient and results in both soluble capsid protein and conical or tubular capsid assemblies, seemingly converted from immature Gag particles. Computer simulations further reveal probable assembly pathways of HIV-1 capsid formation. Combining the experimental data and computer simulations, our results suggest a sequential combination of both displacive and disassembly/reassembly processes for HIV-1 maturation.
authors.affiliation: Department of Structural Biology, University of Pittsburgh School of Medicine, 3501 5th Avenue, Pittsburgh, Pennsylvania 15260, USA.|Pittsburgh Center for HIV Protein Interactions, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15260, USA.
authors.forename: Jiying
authors.initials: J
authors.lastname: Ning
authors.affiliation: Department of Physics and Astronomy, University of California, Riverside, California 92521, USA.
authors.forename: Gonca
authors.initials: G
authors.lastname: Erdemci-Tandogan
authors.affiliation: Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.
authors.forename: Ernest L
authors.initials: EL
authors.lastname: Yufenyuy
authors.affiliation: Department of Physics and Astronomy, University of California, Riverside, California 92521, USA.
authors.forename: Jef
authors.initials: J
authors.lastname: Wagner
authors.affiliation: Department of Structural Biology, University of Pittsburgh School of Medicine, 3501 5th Avenue, Pittsburgh, Pennsylvania 15260, USA.
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Himes
authors.affiliation: Department of Structural Biology, University of Pittsburgh School of Medicine, 3501 5th Avenue, Pittsburgh, Pennsylvania 15260, USA.|Pittsburgh Center for HIV Protein Interactions, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15260, USA.
authors.forename: Gongpu
authors.initials: G
authors.lastname: Zhao
authors.affiliation: Pittsburgh Center for HIV Protein Interactions, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15260, USA.|Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Aiken
authors.affiliation: Department of Physics and Astronomy, University of California, Riverside, California 92521, USA.
authors.forename: Roya
authors.initials: R
authors.lastname: Zandi
authors.affiliation: Department of Structural Biology, University of Pittsburgh School of Medicine, 3501 5th Avenue, Pittsburgh, Pennsylvania 15260, USA.|Pittsburgh Center for HIV Protein Interactions, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15260, USA.|Division of Structural Biology, University of Oxford, The Henry Wellcome Building for Genomic Medicine, Headington, Oxford OX3 7BN, UK.|Electron Bio-Imaging Centre, Diamond Light Sources, Harwell Science and Innovation Campus, Didcot OX11 0DE, UK.
authors.forename: Peijun
authors.initials: P
authors.lastname: Zhang
mesh_terms: D036022:Capsid Proteins / Q000378:metabolism*; D003198:Computer Simulation; D020285:Cryoelectron Microscopy; D015497:HIV-1 / Q000502:physiology* / Q000648:ultrastructure; D014771:Virion / Q000502:physiology; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000378:metabolism
chemical_list: D036022:Capsid Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus