A novel strategy to inhibit the reproduction and translation of hepatitis C virus

Aiping Duan,Limin Ning,Genxi Li,Yafei Hou,Nana Yang,Lizhou Sun,Chao Li

doi:10.1007/s11427-013-4468-2

Abstract

Hepatitis C virus (HCV), a positive single-stranded RNA virus, is a major cause of liver disease in humans. Herein we report a novel strategy to inhibit the reproduction and translation of HCV using a short RNA, named an Additional RNA, to activate the endonuclease activity of Argonaute 2 (Ago2). In the presence of the Additional RNA, the HCV genome RNA has the requisite 12 nucleotides of base-pairing with microRNA-122. This activates the endonuclease activity of Ago2, resulting in cleavage and release of the HCV genome RNA from Ago2 and microRNA-122. The free HCV genome RNA would be susceptible to intracellular degradation, effectively inhibiting its reproduction and translation. This study presents a new method to inhibit HCV that may hold great potential for HCV treatment in the future.

Highlights

Hepatitis C virus (HCV), a positive single-stranded RNA virus, is a major cause of liver disease in humans
We proposed to introduce a short piece of RNA, named an ‘Additional RNA’, to activate the endonuclease activity of Argonaute 2 (Ago2)
When Ago2 cleaves the HCV 5′ untranslated region (UTR), the latter is released from Ago2 and miR-122; the protection of the viral genome is removed and the RNA will be degraded, effectively inhibiting reproduction and translation of HCV

Summary

Introduction

Hepatitis C virus (HCV), a positive single-stranded RNA virus, is a major cause of liver disease in humans. In the presence of the Additional RNA, the HCV genome RNA has the requisite 12 nucleotides of base-pairing with microRNA-122. The free HCV genome RNA would be susceptible to intracellular degradation, effectively inhibiting its reproduction and translation. The PIWI domain has endonucleolytic activity and the PAZ domain binds single-stranded RNA [12,13]. We hypothesized that releasing the HCV genome RNA from Ago and miR-122 might be an effective way to inhibit HCV reproduction and translation, potentially being an efficient way to treat hepatitis C. We have taken advantage of this protein’s endonucleolytic activity to separate the HCV genome RNA from Ago and miR-122

Methods

Results

Conclusion