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Cell cycle kinetic dysregulation in HIV-infected normal lymphocytes.
Asmuth, David M; Wang, Nan; Lu, Ying; Li, Xiao-Dong; Reece, Lisa; Terry, Nicholas H A; Pollard, Richard B; Nokta, Mostafa; Leary, James F; White, R Allen.
Afiliação
  • Asmuth DM; Department of Internal Medicine, University of California-Davis, Sacramento, California. david.asmuth@ucdmc/ucdavis.edu
Cytometry A ; 66(1): 41-51, 2005 Jul.
Article em En | MEDLINE | ID: mdl-15915506
BACKGROUND: Viruses alter cellular gene transcription and protein binding at many steps critical for cell cycle regulation to optimize the milieu for productive infection. Reasoning that virus-host cell interactions would result in perturbations of cell cycle kinetics, measurement of the duration of the phases of the cell cycle in normal T lymphocytes infected with human immunodeficiency virus (HIV) was undertaken. METHODS: Flow cytometric measurement of bromodeoxyuridine-labeled and DNA content-stained cells at multiple points through the cell cycle allowed estimation of the fraction of cells in each phase, the potential doubling-time, and the durations of S and G(2)/M phases. Separate analysis of the HIV(+) and HIV(-) populations within the infected cultures was performed based on intracellular, anti-HIV core p24 antibody labeling. A novel mathematical model, which accounted for cell loss, was developed to estimate cell cycle phases. RESULTS: (a) S phase was prolonged in the HIV-1(SF2)-infected cells compared with control. (b) This delay in S phase was due to delay in the population of cells not expressing HIV-1 antigens (p24 negative). (c) Accumulation of cells in G(2)/M phase was confirmed in HIV-1-infected cultures and was proportional to the level of infection as measured by p24 fluorescent intensity. However, all mock and HIV-1-infected populations predicted to proceed through cell division demonstrated similar G(2)/M-phase durations. (c) Potential doubling times were longer in the infected cultures; in contrast, the p24(+) subpopulations accounted for this delay. This suggests an isolated delay in the G(0)/G(1) phase for that population of cells. CONCLUSIONS: Multiple phases of host cell cycle durations were affected by HIV-1(SF2) infection in this in vitro model, suggesting novel HIV-1 pathogenesis mechanisms. Prolonged S-phase durations in HIV-1 infected/p24(-) and G(0)/G(1)-phase durations in HIV-1 infected/p24(+) subpopulations require further study to identify mechanistic pathways.
Assuntos
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Leucócitos Mononucleares / Ciclo Celular / HIV-1 Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Cytometry A Ano de publicação: 2005 Tipo de documento: Article
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Leucócitos Mononucleares / Ciclo Celular / HIV-1 Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Cytometry A Ano de publicação: 2005 Tipo de documento: Article