Flow cytometry analysis of cell population dynamics and cell cycle during HIV-1 envelope-mediated formation of syncytia in vitro

In Vitro Cell Dev Biol Anim. 2014;50(5):453-63. doi: 10.1007/s11626-013-9724-z. Epub 2014 Jan 18.

Abstract

Cell fusion occurs in physiological and pathological conditions and plays a role in regulation of cell fate. The analysis of cell population dynamics and cell cycle in cell-cell fusion experiments is necessary to determine changes in the quantitative equilibrium of cell populations and to identify potential bystander effects. Here, using cocultures of Jurkat HIV-1 envelope expressing cells and CD4(+) cells as a model system and flow cytometry for the analysis, the number, viability, and cell cycle status of the populations participating in fusion were determined. In 3-day cocultures, a sustained reduction of the number of CD4(+) cells was observed while they showed high viability and normal cell cycle progression; fusion, but not inhibition of proliferation or death, accounted for their decrease. In contrast, the number of Env(+) cells decreased in cocultures due to fusion, death, and an inherent arrest at G1. Most of syncytia formed in the first 6 h of coculture showed DNA synthesis activity, indicating that the efficient recruitment of proliferating cells contributed to amplify the removal of CD4(+) cells by syncytia formation. Late in cocultures, approximately 50% of syncytia were viable and a subpopulation still underwent DNA synthesis, even when the recruitment of additional cells was prevented by the addition of the fusion inhibitor T-20, indicating that a population of syncytia may progress into the cell cycle. These results show that the quantitative analysis of cellular outcomes of cell-cell fusion can be performed by flow cytometry.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / virology
  • Cell Cycle / genetics*
  • Cell Fusion
  • Cell Proliferation / genetics*
  • Coculture Techniques
  • DNA / biosynthesis
  • Flow Cytometry*
  • Giant Cells / cytology*
  • Giant Cells / metabolism
  • HIV-1 / metabolism
  • Humans
  • In Vitro Techniques
  • Jurkat Cells / metabolism
  • Jurkat Cells / virology
  • Viral Envelope Proteins / metabolism

Substances

  • Viral Envelope Proteins
  • DNA