TRANSGENIC EXPRESSION OF HEPATITIS-C VIRUS STRUCTURAL PROTEINS IN THEMOUSE

Although hepatitis C virus (HCV) is a leading cause of morbidity and m ortality worldwide, the role of viral cytopathic effects remains uncle ar. To study the biosynthesis of HCV structural proteins and their pat hogenic role, we constructed transgenic mice, expressing type 1b HCV s tructural proteins (core, E1, and E2) in Liver tissues. Two liver-spec ific promoters were used. The mouse major urinary protein (MUP) promot er has been shown to be developmentally regulated with little or no ex pression in utero but high-level expression after birth. The albumin ( Alb) promoter provides constitutive, high levels of transgenes in live r. Expression of both HCV transgenes was detected in several Lines by Northern blots, HCV-specific reverse transcriptase-polymerase chain re actions (RT-PCR), and Western immunoblotting. Alb HCV lines showed hig her levels of HCV expression than the MUP HCV Lines. Immunohistochemic al analysis revealed a predominantly cytoplasmic presence of core prot ein with occasional nuclear staining, and both cytoplasmic and membran e expression of the E2 protein in the transgenic livers. In both trans genes, the highest levels of both antigens were seen in perivenular he patocytes, suggesting potential processing specificity in those cells. At six months of age, the Livers of all transgenic lineages remained histologically normal. We concluded that HCV structural proteins are n ot directly cytopathic in this animal model.