Cell cycle kinetic dysregulation in HIV-infected normal lymphocytes

David Asmuth, Nan Wang, Ying Lu, Xiao Dong Li, Lisa Reece, Nicholas H A Terry, Richard B Pollard, Mostafa Nokta, James F. Leary, R. Allen White

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

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 G2/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-1SF2-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 G2/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 G0XG1 phase for that population of cells. Conclusions: Multiple phases of host cell cycle durations were affected by HIV-1SF2 infection in this in vitro model, suggesting novel HIV-1 pathogenesis mechanisms. Prolonged S-phase durations in HIV-1 infected/p24- and G0/G 1-phase durations in HIV-1 infected/p24+ subpopulations require further study to identify mechanistic pathways.

Original languageEnglish (US)
Pages (from-to)41-51
Number of pages11
JournalCytometry Part A
Volume66
Issue number1
DOIs
StatePublished - Jul 2005

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Keywords

  • G phase
  • Human immunodeficiency virus type 1 pathogenesis
  • Kinetics
  • S phase
  • Virus-cell interactions

ASJC Scopus subject areas

  • Hematology
  • Cell Biology
  • Pathology and Forensic Medicine
  • Biophysics
  • Endocrinology

Cite this

Asmuth, D., Wang, N., Lu, Y., Li, X. D., Reece, L., Terry, N. H. A., Pollard, R. B., Nokta, M., Leary, J. F., & White, R. A. (2005). Cell cycle kinetic dysregulation in HIV-infected normal lymphocytes. Cytometry Part A, 66(1), 41-51. https://doi.org/10.1002/cyto.a.20148