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Published on: March 2, 2014
Synergistic antiviral effect of a combination of mouse interferon-alpha and interferon-gamma on mouse hepatitis virus
Uichiro Fuchizaki1, Shuichi Kaneko, Yasunari Nakamoto
1Department of Gastroenterology, Kanazawa University Graduate School of Medicine, Ishikawa, Japan.
Abstract:
Although interferon (IFN)-alpha and IFN-gamma have been reported to exhibit a synergistic antiviral effect through the different signaling pathways in vitro, their therapeutic efficacy is not well defined in vivo. The current study was carried out to investigate the combined antiviral effect in a model of mouse hepatitis virus Type 2 (MHV-2) infection, in which fulminant hepatitis is developed. MHV-2 was injected intraperitoneally into 4-week-old ICR mice, IFN or the vehicle was administered intramuscularly for 5 days, and the antiviral effect was evaluated based on survival periods, liver histology, serum alanine transaminase (ALT) levels, and MHV-2 virus titers in the liver tissues. The animals in the group treated with a combination of IFN-alpha and IFN-gamma survived for longer periods than the groups treated with IFN-alpha alone and IFN-gamma alone (IFN-alpha 10(3) (IU/mouse)/-gamma 10(3) vs. IFN-alpha 10(3), P < 0.005; IFN-alpha 10(3)/-gamma 10(3) vs. IFN-gamma 10(3), P < 0.001). This is consistent with the lower levels of hepatocellular necrosis and serum ALT and the decreased titers of MHV-2 virus in the liver tissues (48 hr, P < 0.001; 72 hr, P < 0.001). These findings indicate that a combination of IFN-alpha and IFN-gamma exhibits a synergistic antiviral effect on MHV-2 infection. The biology of MHV-2 is quite different from that of human hepatitis viruses; however, these results suggest the beneficial combined therapy of IFN-alpha and IFN-gamma for the treatment of human viral hepatitis.
Insights
Combination therapy with interferon (IFN)-alpha and IFN-gamma shows synergistic antiviral effects against mouse hepatitis virus Type 2 (MHV-2) in vivo. This combined treatment significantly improves survival and reduces liver damage, suggesting potential for human viral hepatitis treatment.
Area of Science:
- Virology
- Immunology
- Hepatology
Background:
- Interferon-alpha (IFN-α) and Interferon-gamma (IFN-γ) demonstrate synergistic antiviral effects in vitro via distinct signaling pathways.
- The in vivo therapeutic efficacy of combined IFN-α and IFN-γ remains incompletely defined, particularly in models of viral hepatitis.
Purpose of the Study:
- To investigate the combined antiviral efficacy of IFN-α and IFN-γ in a mouse model of MHV-2-induced fulminant hepatitis.
- To evaluate the impact of combination therapy on survival rates, liver histology, serum alanine transaminase (ALT) levels, and viral titers.
Main Methods:
- ICR mice were infected with MHV-2 and treated intramuscularly with IFN-α, IFN-γ, a combination of both, or vehicle for 5 days.
- Antiviral effects were assessed by monitoring survival periods, performing liver histology, measuring serum ALT levels, and quantifying MHV-2 viral titers in liver tissues.
Main Results:
- Mice treated with combined IFN-α and IFN-γ exhibited significantly longer survival periods compared to those receiving either interferon alone.
- Combination therapy resulted in reduced hepatocellular necrosis, lower serum ALT levels, and decreased MHV-2 viral titers in liver tissues at 48 and 72 hours post-infection.
- Statistical analysis confirmed the synergistic antiviral effect of the combined interferon treatment (P < 0.001).
Conclusions:
- Combined administration of IFN-α and IFN-γ demonstrates a synergistic antiviral effect against MHV-2 infection in vivo.
- This combination therapy offers a promising therapeutic strategy for managing viral hepatitis, despite differences between MHV-2 and human hepatitis viruses.
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