Rapid intracellular competition between hepatitis C viral genomes as a result of mitosis

Brian Webster1, Silke Wissing, Eva Herker

  • 1Gladstone Institute of Virology and Immunology, University of California, San Francisco, San Francisco, California, USA.

Journal of Virology
|October 26, 2012
PubMed

Insights

Hepatitis C virus (HCV) infected cells block new infections via intracellular competition. This competition, especially during cell division, limits viral genetic diversity and recombination in vivo.

Area of Science:

  • Virology
  • Molecular Biology
  • Hepatology

Background:

  • Hepatitis C virus (HCV) establishes persistent infections in hepatocytes.
  • HCV-infected cells exhibit resistance to superinfection, a phenomenon known as superinfection exclusion.
  • Superinfection exclusion in HCV is an intracellular process, not mediated by surface receptor downregulation.

Purpose of the Study:

  • To investigate the mechanisms underlying superinfection exclusion in HCV.
  • To explore intracellular competition between co-infecting HCV genomes.
  • To understand the role of cell division in HCV superinfection exclusion.

Main Methods:

  • Utilized cell culture models of HCV infection.
  • Monitored viral RNA replication and genome competition.
  • Analyzed the impact of cellular mitosis on viral genome persistence.

Main Results:

  • Superinfection exclusion occurs intracellularly, likely involving competition for replication resources or host factors.
  • Cell division (mitosis) creates a competitive environment where co-infecting HCV genomes are randomly eliminated.
  • This genome competition leads to the clearance of one viral genome from a cell within 9-12 days.

Conclusions:

  • Identified a novel mechanism of intracellular competition between HCV strains.
  • Cell division plays a critical role in resolving superinfection exclusion.
  • This competition may limit HCV genetic diversity and recombination potential in vivo.

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