Transgenic expression of hepatitis C virus structural proteins in the mouse

被引:108
|
作者
Kawamura, T
Furusaka, A
Koziel, MJ
Chung, RT
Wang, TC
Schmidt, EV
Liang, TJ
机构
[1] MASSACHUSETTS GEN HOSP, CTR CANC, LAB TUMOR BIOL, CHARLESTOWN, MA 02129 USA
[2] MASSACHUSETTS GEN HOSP, DEPT MED, GASTROINTESTINAL UNIT, BOSTON, MA 02114 USA
[3] HARVARD UNIV, SCH MED, BOSTON, MA USA
[4] NIDDK, LIVER DIS SECT, NIH, BETHESDA, MD USA
[5] MASSACHUSETTS GEN HOSP, CHILDRENS SERV, BOSTON, MA 02129 USA
[6] MASSACHUSETTS GEN HOSP, DEPT PEDIAT, BOSTON, MA 02129 USA
关键词
D O I
10.1002/hep.510250437
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Although hepatitis C virus (HCV) is a leading cause of morbidity and mortality worldwide, the role of viral cytopathic effects remains unclear. To study the biosynthesis of HCV structural proteins and their pathogenic role, we constructed transgenic mice, expressing type 1b HCV structural proteins (core, E1, and E2) in Liver tissues. Two liver-specific promoters were used. The mouse major urinary protein (MUP) promoter has been shown to be developmentally regulated with little or no expression in utero but high-level expression after birth. The albumin (Alb) promoter provides constitutive, high levels of transgenes in liver. Expression of both HCV transgenes was detected in several Lines by Northern blots, HCV-specific reverse transcriptase-polymerase chain reactions (RT-PCR), and Western immunoblotting. Alb HCV lines showed higher levels of HCV expression than the MUP HCV Lines. Immunohistochemical analysis revealed a predominantly cytoplasmic presence of core protein with occasional nuclear staining, and both cytoplasmic and membrane expression of the E2 protein in the transgenic livers. In both transgenes, the highest levels of both antigens were seen in perivenular hepatocytes, 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 not directly cytopathic in this animal model.
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页码:1014 / 1021
页数:8
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