Acute hepatic failure in IFN-gamma-deficient BALB/c mice after murine coronavirus infection.
We previously showed that an intraperitoneal infection with mouse hepatitis virus (MHV) persists in interferon-gamma (IFN-gamma)-deficient C57BL/6 (B6-GKO) mice and results in subacute fatal peritonitis, which bears a resemblance to feline infectious peritonitis. To examine the role of other host factors in MHV infection in mice, IFN-gamma-deficient mice with a BALB/c background (BALB-GKO) were infected intraperitoneally with MHV and compared with B6-GKO mice. In contrast to B6-GKO mice, BALB-GKO mice died within 1 week due to acute hepatic failure. The viral titer of the liver in BALB-GKO mice was significantly higher than that in B6-GKO mice. All hepatocytes in BALB-GKO mice were necrotic at 5 days post-infection, which was clearly distinct from large but limited lesion in the liver from infected B6-GKO mice. The serum alanine aminotransferase activity of infected BALB-GKO mice were higher than that of B6-GKO mice and was paralleled with the severity of the pathological changes and viral titers in infected mice. Administration of exogenous IFN-gamma to BALB-GKO partially inhibited the acute death. These results indicate that BALB-GKO and B6-GKO mice clearly show different diseases following MHV infection, although wild type counterparts of both mice apparently showed the same clinical course after MHV infection.
Kyuwa
Shigeru
S
Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan. akyuwa@mail.ecc.u-tokyo.ac.jp
Shibata
Shinwa
S
Tagawa
Yoh-ichi
Y
Iwakura
Yoichiroh
Y
Machii
Kenji
K
Urano
Toru
T
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D018352:Coronavirus Infections / Q000097:blood / Q000276:immunology* / Q000473:pathology / Q000821:virology; D006524:Hepatitis, Viral, Animal / Q000097:blood / Q000276:immunology* / Q000473:pathology / Q000821:virology; D007274:Injections, Intraperitoneal; D007371:Interferon-gamma / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D017114:Liver Failure, Acute / Q000097:blood / Q000276:immunology* / Q000473:pathology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D006517:Murine hepatitis virus / Q000254:growth & development / Q000276:immunology*
D007371:Interferon-gamma; D000410:Alanine Transaminase