Inhibition of hepatitis C virus using siRNA targeted to the virus and Hsp90

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• 作者：Ana Claudia Silva Braga ; Bruno Moreira Carneiro…
• 关键词：Hepatitis C ; Hsp90 ; RNA interference ; siRNA ; HCV ; Heat shock protein
• 刊名：Cell Stress and Chaperones
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：22
• 期：1
• 页码：113-122
• 全文大小：
• 刊物主题：Biomedicine, general; Cell Biology; Biochemistry, general; Immunology; Cancer Research; Neurosciences;
• 出版者：Springer Netherlands
• ISSN：1466-1268
• 卷排序：22

文摘

Hepatitis C (HCV) is a viral disease affecting millions of people worldwide, and persistent HCV infection can lead to progressive liver disease with the development of liver cirrhosis and hepatocellular carcinoma. During treatment for hepatitis C, the occurrence of viral resistance is common. To reduce the occurrence of resistance, new viral treatments should target both viral and cellular factors. Many interactions occur between viral and host proteins during the HCV replication cycle and might be used for the development of new therapies against hepatitis C. Heat shock protein 90 (Hsp90) plays a role in the folding of cellular and viral proteins and also interacts with HCV proteins. In the present study, we knocked down the expression of the Hsp90 gene and inhibited viral replication using siRNA molecules. Reducing the expression of Hsp90 successfully decreased HCV replication. All siRNA molecules specific to the viral genome showed the efficient inhibition of viral replication, particularly siRNA targeted to the 5′UTR region. The combination of siRNAs targeting the viral genome and Hsp90 mRNA also successfully reduced HCV replication and reduced the occurrence of viral resistance. Moreover, these results suggest that an approach based on the combination of cellular and viral siRNAs can be used as an effective alternative for hepatitis C viral suppression.