Molecular Dissection of Hepatitis C Virus Expression

Objective: The 5′ untranslated region (5′ UTR) of the hepatitis C virus genome is thought to be important for the control of viral gene expression and a likely target for therapeutic interception. A functional role of this viral gene segment was analyzed both in vivo and in vitro. Methods: Transgenic mice carrying a reporter gene that contains the complete 5′ UTR sequence were made. Cellular protein(s) which associate with the 5′ UTR were analyzed by gel shift analysis and a following affinity purification. Results: Transgenic mice revealed protein accumulation only in periportal hepatocytes around the portal triad and not in perivenous hepatocytes around the central vein. Gel shift analysis using mouse liver extracts provides further evidence that trans-acting proteins, which recognize a specific cis-acting element with the 5′ UTR (an apparent stemmed structure formed by two noncontiguous RNA sequences), are present in adult mice but not in young mice. A similar 5′ UTR RNA-protein complex was also detected with human liver extracts. Conclusion: The presence of cellular factor(s) which allow HCV 5′ UTR to express in tissue and differentiation state-specific manner was suggested.

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