Resistance of lymphocytic choriomeningitis virus to alpha/beta interferon and to gamma interferon
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D Moskophidis1, M Battegay, M A Bruendler
1Institute of Experimental Immunology, University of Zurich, Switzerland.
Abstract:
The susceptibility to alpha/beta interferon (IFN-alpha/beta) or to gamma interferon (IFN-gamma) of various lymphocytic choriomeningitis virus (LCMV) strains was evaluated in C57BL/6 mice and in various cell lines. Anti-IFN-gamma treatment in vivo revealed that the LCMV strains Armstrong, Aggressive, and WE were most susceptible to IFN-gamma whereas Traub, Cl 13-Armstrong, and Docile were resistant. The same pattern of susceptibility to recombinant IFN-gamma was observed in vitro. In vivo treatment with anti-IFN-alpha/beta showed a sizeable increase in replication of Aggressive, Armstrong, and WE; effects were less pronounced for Docile, Cl 13-Armstrong, or Traub. Correspondingly, WE, Armstrong, and Aggressive were all relatively sensitive to purified IFN-alpha/beta in vitro, and Cl 13-Armstrong, Docile, and Traub were more resistant. Overall, there was a good correlation between the capacity of LCMV strains to establish a persistent infection in adult immunocompetent mice and their relative resistance to IFN-gamma and IFN-alpha/beta.
Insights
This study shows that lymphocytic choriomeningitis virus (LCMV) strains resistant to interferon-gamma and interferon-alpha/beta are more likely to cause persistent infections in mice.
Area of Science:
- Virology
- Immunology
- Infectious Diseases
Background:
- Lymphocytic choriomeningitis virus (LCMV) is a significant pathogen with diverse strains.
- Interferons (IFNs) are critical cytokines in antiviral immunity.
- Understanding LCMV strain variation in IFN susceptibility is key to controlling infections.
Purpose of the Study:
- To evaluate the susceptibility of different LCMV strains to interferon-alpha/beta (IFN-alpha/beta) and interferon-gamma (IFN-gamma).
- To correlate LCMV strain IFN susceptibility with the ability to establish persistent infections in immunocompetent mice.
Main Methods:
- Assessed LCMV strain susceptibility to IFN-gamma and IFN-alpha/beta in vivo using C57BL/6 mice and in vitro using cell lines.
- Administered anti-IFN-gamma and anti-IFN-alpha/beta treatments to mice to assess viral replication.
- Compared IFN susceptibility patterns across multiple LCMV strains (Armstrong, Aggressive, WE, Traub, Cl 13-Armstrong, Docile).
Main Results:
- LCMV strains Armstrong, Aggressive, and WE were highly susceptible to IFN-gamma, while Traub, Cl 13-Armstrong, and Docile were resistant.
- In vivo and in vitro IFN-gamma susceptibility mirrored this pattern.
- Replication of Armstrong, Aggressive, and WE increased significantly after anti-IFN-alpha/beta treatment, indicating sensitivity.
- Cl 13-Armstrong, Docile, and Traub showed less pronounced increases, indicating resistance to IFN-alpha/beta.
- A strong correlation was observed between resistance to both IFN-gamma and IFN-alpha/beta and the capacity of LCMV strains to establish persistent infections.
Conclusions:
- LCMV strain resistance to both IFN-gamma and IFN-alpha/beta is a critical factor in establishing persistent infections.
- These findings highlight the role of innate immune responses, particularly interferons, in controlling LCMV infection outcomes.
- Differential IFN susceptibility among LCMV strains contributes to their varying pathogenetic potential.