Liver impairment in murine hepatitis virus 3 induced murine severe acute respiratory syndrome model / 中华传染病杂志

ABSTRACT

Objectives To investigate dynamic pathological features and virus distribution in the liver with a murine severe acute respiratory syndrome(SARS)model injected with murine hepati- tis virus 3(MHV-3)through trachea.As a representative of host genes,mouse fgl2(mfgl2)pro- thrombinase gene expression and its clinical significance were discussed in SARS associated liver dam- ages.Methods The Balb/cJ mice were infected with 100 PFU of MHV-3 through trachea and Balb/ cJ mice injected with saline were served as control.Survival rate,pathological features in organs and liver function were observed.Virus titers in different organs were determined on monolayer of L2 cells by a standard plaque assay.Virus distribution and cellular localization were studied by in situ hy- bridization.Both mfgl2 and fibrin expressions were examined in the liver by in situ hybridization and immunohistochemistry to investigate the role of mfgl2 in the liver impairment.Results Mice infected with MHV-3 through trachea developed multiple organs damages and died within 5 days,while all mice in control group survived with no histopathological changes.Infected liver tissues showed wide- spread cloudy swelling,prominent ballooning degeneration with mild lymphocytic infiltration in the portal area.Dot and zonal hepatocellular necrosis could be found occasionally.The lungs showed typi- cal interstitial pneumonia and hyaline membranes formation.Other histological changes also could be found in other organs examined.MHV-3 virus replication was identified in all organs observed.The liver function was injured,mfgl2 expression were evidenced mainly in the necrosis areas with fibrin deposition around the necrosis areas.Conclusions Pathological changes of the liver in this murine SARS model can mimic the liver impairment characteristics of SARS in human.In addition to the physical damage induced by the virus,the up-regulation of novel gene mfgl2 in the liver in association with fibrin deposition may play a vital role in the development of SARS associated liver damages.