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.
- G phase
- Human immunodeficiency virus type 1 pathogenesis
- S phase
- Virus-cell interactions
ASJC Scopus subject areas
- Cell Biology
- Pathology and Forensic Medicine