Inducible nitric oxide synthase (iNOS) expression in liver and splenic T lymphocyte rise are associated with liver histological damage during experimental hepatitis A virus (HAV) infection in Callithrix jacchus

Callithrix jacchus is considered a reliable animal model for hepatitis A vi rus (HAV) infection. All three HAV orally inoculated marmosets developed he patitis - the infection was monitored by continuous virus shedding, high le vels of serum enzyme alanine aminotransferase, specific antibody and seroco nversion 3-6 weeks after HAV inoculation. HAV antigen was detected in liver by immunofluorescence 4 days post inoculation (PI) and onwards. To gain in sight into the biological role of inducible nitric oxide synthase (iNOS) du ring immune-related acute liver injury the enzyme was searched in frozen bi opsies; immunofluorescent labeling was found in the cytoplasm of liver cell s mainly Kupffer's cells and spleen macrophages (CD68+) starting 11 days PI with maximum intensity on the fifth to sixth week PI. Necroinflammatory li ver lesions characteristic of viral hepatitis were also observed at 10 days PI with maximum severity at 4 to 6 weeks PI. Furthermore, T lymphocytes (C D2+) were raised at this time point. No difference was evident in the frequ ency of B lymphocytes (CD20+). Therefore, iNOS expression preceded necroinf lammatory liver lesion and maximal immunofluorescence reaction was coincide nt with tissue injury, supporting the hypothesis that NO contributes to hep atic cytotoxic mechanism but also to virus clearance. The concomitant rise in T-lymphocyte population may suggest a role for these cells in this and/o r other independent HAV-induced pathological changes.