Persistent infection with mouse hepatitis virus 3 in mouse lymphoid cell lines

Area of Science:

• Virology
• Immunology
• Cell Biology

Background:

• Mouse hepatitis virus 3 (MHV3) sensitivity varies in mice.
• MHV3 survivors can develop chronic disease with paralysis and immunodeficiency.
• Persistent MHV3 infections in lymphoid cells show virus production and cell lysis.

Purpose of the Study:

• Characterize persistent MHV3 infections in vitro.
• Investigate viral transmission mechanisms in cell cultures.
• Analyze biological and biochemical properties of MHV3 variants from persistent infections.

Main Methods:

• Established persistent MHV3 infections in YAC and RDM-4 mouse lymphoid cell lines.
• Monitored virus production, antigen presence, and cell lysis.
• Utilized cell cloning and antibody treatment to study viral transmission.
• Characterized MHV3 variants for thermosensitivity and pathogenicity in vivo.

Main Results:

• Persistent MHV3 infection in lymphoid cells led to cell lysis and decreased virus titers during "crisis" phases.
• Viral transmission occurred via infection of newly permissive cells, not by infected dividing cells.
• MHV3 variants from lymphoid cells showed heterogeneity but no selection of temperature-sensitive mutants.
• MHV3 rapidly lost pathogenicity in mice, inducing subclinical infections and defense mechanisms.

Conclusions:

• MHV3 replication in lymphoid cell lines induces or selects variants.
• These variants maintain in vitro pathogenicity but have reduced pathogenic effects in vivo.
• This suggests a mechanism for reduced MHV3 virulence after lymphoid cell adaptation.