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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.

SUBMITTER: Lingappa JR

PROVIDER: S-EPMC4351045 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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How HIV-1 Gag assembles in cells: Putting together pieces of the puzzle.

Lingappa Jaisri R JR Reed Jonathan C JC Tanaka Motoko M Chutiraka Kasana K Robinson Bridget A BA

Virus research 20140724

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 ...[more]

PMID: 25066606

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Project description:BackgroundConflicting research emphasizes depression, diabetes distress, or well-being in relation to diabetes self-care and risk for poor health outcomes.PurposeThe purpose of this study was to test whether a latent variable for general psychological distress derived from shared variance of depression symptoms, diabetes distress, and well-being predicts a latent variable of diabetes self-care and to examine evidence for unique effects once shared effects are adjusted for.MethodsAdults with suboptimally controlled diabetes were recruited from the South Bronx, NY, for a telephonic diabetes self-management support trial. Baseline diabetes self-care, medication adherence, depression symptoms, diabetes distress, and well-being were measured by validated self-report. Structural equation modeling specified a latent variable for general psychological distress derived from shared variance of depression symptoms, diabetes distress, and well-being. Diabetes self-care was a latent variable indicated by diet, glucose self-monitoring, and medication adherence.ResultsParticipants (N = 627, 65% female) were predominantly ethnic minority (70% Hispanic; 45% Black) and 77% reported household income <$20K/year. Mean (standard deviation) age = 56 (12) years; A1c = 9.1% (1.9%); body mass index = 32 (8) kg/m2. The latent variable for psychological distress was a robust predictor of poorer diabetes self-care (coefficient = -0.59 [confidence interval = -0.71, -0.46], p < .001) with good model fit. Unique paths from depression symptoms, diabetes distress, and well-being (all ps > .99) to self-care were not observed.ConclusionsIn this population of disadvantaged adults with suboptimally controlled diabetes, general psychological distress was strongly associated with poorer diabetes self-care and fully accounted for the effects of depression, diabetes distress, and positive well-being. This suggests that general distress may underlie previously reported associations between these constructs and diabetes self-care.

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How HIV-1 Gag assembles in cells: Putting together pieces of the puzzle.

Publications

How HIV-1 Gag assembles in cells: Putting together pieces of the puzzle.

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