Abstract
BackgroundHepatitis C virus (HCV), a member of the Flaviviridae family of viruses, is a major cause of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Currently, the only treatment available consists of a combination of Pegylated interferon alpha (INF-α) and ribavirin, but only half of the patients treated show a sufficient antiviral response. Thus there is a great need for the development of new treatments for HCV infections. RNA interference (RNAi) represents a new promising approach to develop effective antiviral drugs and has been extremely effective against HCV infection.ResultsThis study was design to assess or explore the silencing effect of small interference RNAs (siRNAs) against full length HCV particles of genotype 1a. In the present study six 21-bp siRNAs were designed against different regions of HCV structural genes (Core, E1 and E2). Selected siRNAs were labeled as Csi 301, Csi 29, E1si 52, E1si 192, E2si 86 and E2si 493. Our results demonstrated that siRNAs directed against HCV core gene showed 70% reduction in viral titer in HCV infected liver cells. Moreover, siRNAs against E1 and E2 envelop genes showed a dramatic reduction in HCV viral RNA, E2si 86 exhibited 93% inhibition, while E1si 192, E2si 493 and E1si 52 showed 87%, 80%, and 66% inhibition respectively. No significant inhibition was detected in cells transfected with the negative control siRNA.ConclusionOur results suggested that siRNAs targeted against HCV structural genes efficiently silence full length HCV particles and provide an effective therapeutic option against HCV infection.
Highlights
Hepatitis C virus (HCV), a member of the Flaviviridae family of viruses, is a major cause of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma
Silencing effect of small interference RNAs (siRNAs) on liver infected cells The ability of siRNAs to inhibit HCV replication and infection was evaluated by designing and constructing siRNAs against different sites of HCV structural genes having genotype1a (Core, E1 and E2). siRNAs targeting sites were selected in regions conserved among different samples
The results indicate that siRNAs targeting HCV structural genes have the ability to inhibit the whole virus of 1a genotype in serum infected liver cells
Summary
Hepatitis C virus (HCV), a member of the Flaviviridae family of viruses, is a major cause of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. There is a great need for the development of new treatments for HCV infections. RNA interference (RNAi) represents a new promising approach to develop effective antiviral drugs and has been extremely effective against HCV infection. HCV was identified in 1989 as the leading pathogen for non-A, non-B viral hepatitis [1]. HCV is an enveloped positive-single stranded RNA virus 9.6 kb in length consisting of structural (Core, E1, E2 and possibly p7) proteins and nonstructural (NS2, NS3, NS4A, NS4B, NS5A and NS5B) proteins [2,3]. HCV Core is known as the inducer of steatosis, oxidative stress and liver cancer [4].
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