Immunopathology of Mouse Hepatitis Virus Type 3 Infection

Prévost, C. Le; Lévy-Leblond, E.; Virelizier, J L; Dupuy, J. M.

doi:10.4049/jimmunol.114.1_part_1.221

Cited by 64 publications

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The Effect of Mouse Hepatitis Virus Infection on the Microcirculation of the Liver

et al. 2007

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Mouse hepatitis virus type 3 infection results in strain-dependent liver disease. The effects of mouse hepatitis virus type 3 on the microcirculation of the liver in both fully susceptible (Balb/cJ) and fully resistant (A/& mice were studied. In Balb/cJ mice, 6 to 12 h r following infection, abnormalities in liver blood flow were observed which consisted of granular blood flow in both terminal hepatic and terminal portal venules. In addition, sinusoidal microthrombi were present predominantly in periportal areas. By 24 to 48 hr, liver cell edema and small focal lesions were prominent. At 48 hr, thrombi and hepatocellular necrosis were widespread, and blood was shunted from damaged areas into patent sinusoids. In sharp contrast to these abnormal findings, normal streamlined blood flow was present in the resistant A/J animals at all time points following infection. Since large amounts of virus were demonstrated by immunofluorescene in and by recovery and growth from livers of both resistant and susceptible strains, the presence of the virus per se cannot explain the abnormalities observed.

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The Effect of Mouse Hepatitis Virus Infection on the Microcirculation of the Liver

et al. 2007

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Recovery from Mouse Hepatitis Virus Infection Depends on Recruitment of CD8+ Cells Rather Than Activation of Intrahepatic CD4+αβ−TCRinter or NK-T Cells

Lamontagne

Lusignan

Page

2001

Clinical Immunology

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Mouse hepatitis virus (MHV) provides an excellent animal model for the study of the immunopathological mechanisms involved in hepatic viral diseases. We previously generated an attenuated viral variant, YAC-MHV3, which induces a subclinical disease and recovery within 15 days. In contrast, the L2-MHV3 strain induces the development of a fulminant hepatitis, leading to death within 3 days. In this paper, we document intrahepatic and splenic T cell subpopulations involved in the hepatitis process and viral elimination identified in attenuated or pathogenic MHV3-infected C57BL/6 mice. Percentages of intrahepatic CD4(+) cells decreased in attenuated YAC-MHV3-infected mice, while they increased in mice infected with pathogenic L2-MHV3, compared with uninfected animals. Moreover, in YAC-MHV3-infected mice, the percentages of intrahepatic CD8(+) cells slightly decreased at 24 h pi, then increased until 15 days pi. In contrast, the CD4/CD8 ratios of splenic lymphoid subpopulations increased in the first days of infection and returned to normal values at 15 days pi. Intrahepatic NK1.1(+)alphabeta - TCR(inter) cells decreased in both virally infected groups of mice, while CD4(+)alphabeta - TCR(inter) LFA-1(high) cells increased in L2-MHV3-infected mice, in contrast with what was seen in YAC-MHV3-infected mice. However, these cells became anergic following Con A or PHA stimulation. Ex vivo studies showed that only the intrahepatic CD8(+) cells that were increased in YAC-MHV3-infected mice could be stimulated by lectins. In addition, in vitro viral infections revealed that L2-MHV3 viral infection led to an increase of intrahepatic CD4(+)alphabeta - TCR(inter) cells in the absence of CD8(+) cells only. These results indicate that the attenuated phenotype of the YAC-MHV3 virus is related to two different mechanisms: the first involves no increase of intrahepatic CD4(+)alphabeta - TCR(inter) or NK-T cells, while the second favors the recruitment and activation of CD8(+) cells in liver. The results are discussed in relation to the integrity of intrahepatic immune tolerance mechanisms and immune-mediated viral elimination.

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Treatment of Resistant A/J Mice with Methylprednisolone (MP) Results in Loss of Resistance to Murine Hepatitis Strain 3 (MHV-3) and Induction of Macrophage Procoagulant Activity (PCA)

Fingerote

Leibowitz²,

Rao

et al. 1995

Advances in Experimental Medicine and Biology

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BALB/cJ mice die of fulminant hepatitis within 7 days of exposure to murine hepatitis virus strain 3 (MHV-3) whereas A/J mice are fully resistant to the lethal effects of MHV-3 infection. Previous studies have implicated macrophage activation with production of a unique macrophage prothrombinase (PCA) and lymphocyte cytokine secretion in the pathogenesis of MHV-3 susceptibility and have demonstrated that immunosuppression induces susceptibility in resistant mice. This study was undertaken to determine whether macrophages, derived from resistant A/J mice and treated in vitro with methylprednisolone sodium succinate (MP), elaborated PCA following MHV-3 exposure and whether therapy with MP altered resistance of A/J mice to MHV-3 infection in vivo.Macrophages, incubated with MP in vitro, expressed dose dependent increases in PCA following infection with MHV-3. No induction of PC A occurred in macrophages treated with MHV-3 or MP alone. Analysis ofmRNA transcripts for mouse fibrinogen like protein (musfiblp), the MHV-3 specific prothrombinase, in macrophages which were incubated with MP prior to exposure to MHV-3 demonstrated significantly increased mRNA levels as compared to macrophages not incubated with MP prior to MHV-3 exposure. In vivo, A/J mice treated for 3 days with 500 mg/kg/day of MP prior to infection with MHV-3 demonstrated extensive hepatocyte necrosis and fibrin deposition in hepatic sinusoids on histologi- cal examination of liver tissue, elevated serum transaminases and 100% mortality within 10 days of infection. These results therefore provide further support for the role of increased PCA in the pathogenesis ofMHV-3 related liver necrosis.

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Immunopathology of Mouse Hepatitis Virus Type 3 Infection

Cited by 64 publications

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The Effect of Mouse Hepatitis Virus Infection on the Microcirculation of the Liver

The Effect of Mouse Hepatitis Virus Infection on the Microcirculation of the Liver

Recovery from Mouse Hepatitis Virus Infection Depends on Recruitment of CD8+ Cells Rather Than Activation of Intrahepatic CD4+αβ−TCRinter or NK-T Cells

Treatment of Resistant A/J Mice with Methylprednisolone (MP) Results in Loss of Resistance to Murine Hepatitis Strain 3 (MHV-3) and Induction of Macrophage Procoagulant Activity (PCA)

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