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Restricted Semliki Forest virus replication in perforin and Fas-ligand double-deficient mice
Mohammed Alsharifi1, Mario Lobigs1, Jayaram Bettadapura1
1Division of Immunology and Genetics, The John Curtin School of Medical Research, Australian National University, Canberra, ACT 0200, Australia.
Abstract:
Previously, we have shown that mice defective in granule exocytosis and/or Fas.L/Fas-mediated cytolytic pathways are significantly more resistant to alphavirus, Semliki Forest virus (SFV), infection compared with wild-type mice. Here, we evaluated SFV replication in different tissues of mice defective in both cytolytic pathways (perf(-/-)xgld) relative to that in wild-type counterparts and found that viral replication in perf(-/-)xgld mice is remarkably restricted. Although the mechanism responsible for this observation is yet to be established, the lower virus titres found in these mice indicate that the role of cytolytic effector molecules in antiviral immunity needs to be re-evaluated.
Insights
Mice lacking key immune pathways show strong resistance to Semliki Forest virus (SFV) infection. This suggests a crucial, yet re-evaluated, role for these cytolytic effector molecules in controlling alphavirus replication.
Area of Science:
- Immunology
- Virology
- Infectious Diseases
Background:
- Granule exocytosis and Fas.L/Fas pathways are critical for immune responses.
- Previous studies indicated resistance to alphavirus infection in mice with defects in these pathways.
Purpose of the Study:
- To investigate Semliki Forest virus (SFV) replication in mice lacking both granule exocytosis and Fas.L/Fas-mediated cytolytic pathways (perf(-/-)xgld).
- To compare viral replication in these deficient mice with wild-type counterparts.
Main Methods:
- Evaluation of SFV replication across different tissues.
- Comparison of virus titers between perf(-/-)xgld mice and wild-type mice.
Main Results:
- SFV replication was significantly restricted in perf(-/-)xgld mice compared to wild-type mice.
- Lower virus titers were observed in the tissues of mice with combined defects in cytolytic pathways.
Conclusions:
- The study highlights a remarkable restriction of alphavirus replication in mice lacking key cytolytic immune mechanisms.
- These findings necessitate a re-evaluation of the role of cytolytic effector molecules in antiviral immunity against alphaviruses.
