Interferon enhances the fragility of lysosomes in L-929 mouse fibroblasts

Area of Science:

• Cell Biology
• Virology
• Immunology

Background:

• Interferon (IFN) is a crucial component of the innate immune system, known for its antiviral properties.
• L-929 mouse fibroblasts are a common cell line used in research for studying cellular responses to viral infections and therapeutic agents.
• Vaccinia virus, a large double-stranded DNA virus, is often used as a model to study viral pathogenesis and host-cell interactions.

Purpose of the Study:

• To investigate the mechanism of severe cytolysis observed in L-929 mouse fibroblasts upon infection with vaccinia WR virus after interferon treatment.
• To determine the role of lysosomal enzymes in the observed cytolysis.
• To explore the direct effect of homologous interferon on lysosomes in this experimental model.

Main Methods:

• Infection of L-929 mouse fibroblasts with vaccinia WR virus.
• Treatment of cells with homologous interferon prior to viral infection.
• Assessment of cytolysis and investigation of lysosomal integrity and enzyme release.

Main Results:

• Severe cytolysis occurred within 3 to 4 hours in interferon-treated L-929 cells infected with vaccinia WR virus.
• The released lysosomal enzymes into the cytosol were not the cause of the observed cytolysis.
• Evidence suggests that homologous interferon exerts a direct detrimental effect on lysosomes.

Conclusions:

• The severe cytolysis in interferon-treated, vaccinia virus-infected fibroblasts is not mediated by lysosomal enzyme release into the cytosol.
• Homologous interferon appears to directly damage lysosomes, contributing to cell death.
• This lysosomal damage represents a novel anticellular function of interferon, beyond its direct antiviral effects.