High-fat-induced nonalcoholic fatty liver potentiates vulnerability to and the severity of viral hepatitis in a C3H/HeN mouse model.

Although the concomitance of nonalcoholic fatty liver disease (NAFLD) and viral hepatitis is soaring, there is not much knowledge about the impact of NAFLD on viral hepatitis. Here, we aimed to investigate how NAFLD influences the pathogenesis of viral hepatitis. Wild-type C3H/HeN mice with NAFLD induced by high-fat diet were infected with murine hepatitis virus 3 (MHV-3) and sacrificed at Days 4, 8, 12, and 16 post infection. Although there was no difference in the survival rate between mice with and without NAFLD, individuals with steatosis suffered more severe and prolonged liver injury demonstrated by transaminases and histology examination. The intrahepatic viral load was higher in NAFLD group during early infection, although it declined ultimately. On the contrary, the serum antiviral antibody titer remained in a lower level in mice with NAFLD throughout the investigation. In NAFLD group, the production of proinflammatory cytokines (tumor necrosis factor α, interleukin 1ß, interleukin 6, and interleukin 17A) and the frequencies of antiviral immune cells (NKG2D+ NK cells and CD69+ cytotoxic T lymphocytes [CTLs]) were profoundly increased. Parallelly, the production of anti-inflammatory cytokine (interleukin 10) and inhibitory checkpoint expression (NKG2A on NK cells and programmed cell death-1 on CTLs) were also significantly elevated to maintain homeostasis. However, the upregulation of interleukin 22, a protective cytokine was deficient in NAFLD group post MHV-3 infection. Conclusively, hepatic lipid metabolic abnormalities disturb antiviral immunity and increase the vulnerability to and severity of viral hepatitis.

Correlation of fgl2 prothrombinase gene expression with pulmonary impairment in the murine model of severe acute respiratory syndrome / 医学研究生学报

Objective: To investigate the relationship of murine fibrinogen-like protein 2(mfgl2) / fibroleukin with pulmonary impairment in the murine model of severe acute respiratory syndrome(SARS).Methods: The Balb/cJ mice infected with murine hepatitis virus strain 3(MHV-3) through the trachea were observed for the pathological features and virus distribution in different organs.The expressions of both mfgl2 and fibrino in the lungs were determined by in situ hybridization and immunohistochemistry.Results: The MHV-3 infected mice developed typical interstitial pneumonia with extensive hyaline membrane formation in the alveoli,presented micro-vascular thrombosis in the pulmonary vessels and died within 5 days.MHV-3 virus replication was identified in all the organs observed.The specific expression of mfgl2 prothrombinase was noted in the terminal and respiratory bronchioles,alveolar epithelia and infiltrating cells.Conclusion: The characteristics of the pulmonary impairment of SARS in human can be properly simulated by the MHV-3 induced murine model of SARS.The up-regulation of the specific gene mfgl2 in the lungs involved in fibrino deposition and microvascular thrombosis may be largely responsible for SARS-associated pulmonary damages.