Synergistic antiviral effect of a combination of mouse interferon-alpha and interferon-gamma on mouse hepatitis virus - PubMed (original) (raw)

Synergistic antiviral effect of a combination of mouse interferon-alpha and interferon-gamma on mouse hepatitis virus

Uichiro Fuchizaki et al. J Med Virol. 2003 Feb.

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.

PubMed Disclaimer

References

    1. Allen G, Diaz MO. 1996. Nomenclature of the human interferon proteins. J Interferon Cytokine Res 16: 181–184. - PubMed
    1. Bergamini A, Bolacchi F, Cepparulo M, Demin F, Uccella I, Bongiovanni B, Ombres D, Angelico F, Liuti A, Hurtova M, Francioso S, Carvelli C, Cerasari G, Angelico M, Rocchi G. 2001. Treatment with ribavirin and interferon‐alpha reduces interferon‐gamma expression in patients with chronic hepatitis C. Clin Exp Immunol 123: 459–464. - PMC - PubMed
    1. Carlowitz I, Bellon L, Tong MJ, Conrad A, Pavco PA, Blatt LM. 2000. Inhibition of hepatitis C virus (HCV)‐RNA‐dependent translation and replication of a chimeric HCV poliovirus using synthetic stabilized ribozymes. Hepatology 31: 769–776. - PubMed
    1. Compton SR, Barthold SW, Smith AL. 1993. The cellular and molecular pathogenesis of coronavirus. Lab Anim 43: 15–28. - PubMed
    1. Darnell JE Jr, Kerr IM, Stark GR. 1994. Jak‐STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. Science 264: 1415–1421. - PubMed

MeSH terms

Substances

LinkOut - more resources