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Molecular anatomy of mouse hepatitis virus persistence: coevolution of increased host cell resistance and virus

W Chen1, R S Baric

  • 1Department of Epidemiology, Program in Infectious Diseases, University of North Carolina at Chapel Hill, 27599-7400, USA.

Journal of Virology
|June 1, 1996
PubMed

Insights

Persistent mouse hepatitis virus (MHV) infection in cells involves reduced MHV receptor (MHVR) expression, leading to host resistance. Coevolving viruses gain increased MHVR avidity and utilize alternative receptors.

Area of Science:

  • Virology
  • Cell Biology
  • Immunology

Background:

  • Persistent viral infections are a significant challenge in medicine.
  • Understanding virus-host interactions is crucial for developing antiviral strategies.
  • Mouse hepatitis virus (MHV) provides a model system for studying persistent infections.

Purpose of the Study:

  • To investigate the mechanisms underlying persistent MHV infection in vitro.
  • To identify alterations in virus-host interactions during the development of host resistance.
  • To explore the coevolution of virus virulence and host cell resistance.

Main Methods:

  • Establishing a persistent MHV infection model using murine astrocytoma (DBT) cells.
  • Quantifying MHV receptor (MHVR) expression in infected and resistant cell populations.
  • Assessing viral replication capacity in host cells with varying MHVR expression levels.
  • Transfecting MHVR into resistant cells to evaluate restoration of viral replication.

Main Results:

  • Persistent MHV infection was mediated by reduced MHVR expression and increased virus virulence.
  • MHV persistence selected for resistant host cell populations that abated viral replication.
  • Reduced MHVR expression correlated with increased host resistance.
  • MHVR transfection restored efficient MHV replication in resistant cells.
  • Variant viruses emerged with increased MHVR avidity and recognition of alternative receptors.

Conclusions:

  • MHV persistence in vitro is mediated by cellular MHVR expression and viral virulence.
  • Host cell resistance to MHV involves reduced MHVR expression, which can be overcome by MHVR transfection.
  • Virus-host interactions at the cellular level are critical in the evolution of host resistance and viral coevolution.
  • This in vitro system serves as a valuable model for studying virus-host dynamics during persistent infections.

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