title: How HIV-1 Gag assembles in cells: Putting together pieces of the puzzle.
abstract: During the late stage of the viral life cycle, HIV-1 Gag assembles into a spherical immature capsid, and undergoes budding, release, and maturation. Here we review events involved in immature capsid assembly from the perspective of five different approaches used to study this process: mutational analysis, structural studies, assembly of purified recombinant Gag, assembly of newly translated Gag in a cell-free system, and studies in cells using biochemical and imaging techniques. We summarize key findings obtained using each approach, point out where there is consensus, and highlight unanswered questions. Particular emphasis is placed on reconciling data suggesting that Gag assembles by two different paths, depending on the assembly environment. Specifically, in assembly systems that lack cellular proteins, high concentrations of Gag can spontaneously assemble using purified nucleic acid as a scaffold. However, in the more complex intracellular environment, barriers that limit self-assembly are present in the form of cellular proteins, organelles, host defenses, and the absence of free nucleic acid. To overcome these barriers and promote efficient immature capsid formation in an unfavorable environment, Gag appears to utilize an energy-dependent, host-catalyzed, pathway of assembly intermediates in cells. Overall, we show how data obtained using a variety of techniques has led to our current understanding of HIV assembly.
authors: Department of Global Health, University of Washington, Seattle, WA, United States; Departments of Medicine and Microbiology, University of Washington, Seattle, WA, United States. Electronic address: jais@u.washington.edu.
authors: Jaisri R
authors: JR
authors: Lingappa
authors: Department of Global Health, University of Washington, Seattle, WA, United States. Electronic address: reedjon@u.washington.edu.
authors: Jonathan C
authors: JC
authors: Reed
authors: Department of Global Health, University of Washington, Seattle, WA, United States. Electronic address: mt1982@u.washington.edu.
authors: Motoko
authors: M
authors: Tanaka
authors: Department of Global Health, University of Washington, Seattle, WA, United States. Electronic address: jadukdik@uw.edu.
authors: Kasana
authors: K
authors: Chutiraka
authors: Department of Global Health, University of Washington, Seattle, WA, United States. Electronic address: robinsob@u.washington.edu.
authors: Bridget A
authors: BA
authors: Robinson
mesh_terms: D036022:Capsid Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D002474:Cell-Free System; D055785:Gene Knockdown Techniques; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D057054:Molecular Imaging; D009154:Mutation; D054730:Protein Interaction Domains and Motifs; D034622:RNA Interference; D013329:Structure-Activity Relationship; D019065:Virus Assembly; D014779:Virus Replication; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D036022:Capsid Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus
keywords: Assembly intermediates; Gag; HIV-1; Immature capsid; Retrovirus; Virus assembly