Tags

Type your tag names separated by a space and hit enter

Post-transcriptional inhibition of hepatitis C virus replication through small interference RNA.
Virol J. 2011 Mar 10; 8:112.VJ

Abstract

BACKGROUND

Hepatitis C Virus (HCV) infection is a major health problem throughout world that causes acute and chronic infection which resulted in liver fibrosis, hepatocellular carcinoma and death. The only therapy currently available for HCV infection is the combination of pegylated interferon alpha (PEG-IFN α) and ribavirin. This therapy can effectively clear the virus infection in only 50% of infected individuals. Hence, there is a dire need to develop antiviral agents against HCV.

RESULTS

This study was design to examine the ability of exogenous small interfering RNAs (siRNAs) to block the replication of HCV in human liver cells. In the present study six 21-bp siRNAs were designed against different regions of HCV non-structural genes (NS2, NS3 serine protease/helicase, NS4Band NS5B RNA dependent RNA polymerase). siRNAs were labeled as NS2si241, NS3si-229, NS3si-858, NS4Bsi-166, NS5Bsi-241 and NS5Bsi-1064. We found that siRNAs against HCV NS2- NS5B efficiently inhibit HCV replication in Huh-7 cells. Our results demonstrated that siRNAs directed against HCV NS3 (NS3si-229 and NS3si-858) showed 58% and 88% reduction in viral titer respectively. Moreover, NS4Bsi-166 and NS5Bsi-1064 exhibited a dramatic reduction in HCV viral RNA and resulted in greater than 90% inhibition at a 20 μM concentration, while NS2si-241 showed 27% reduction in viral titer. No significant inhibition was detected in cells transfected with the negative control siRNA.

CONCLUSION

Our results suggest that siRNAs targeting against HCV non-structural genes (NS2-NS5B) efficiently inhibit HCV replication and combination of these siRNAs of different targets and interferon will be better option to treat HCV infection throughout the world.

Authors+Show Affiliations

Division of Molecular Medicine, National Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan. usmancemb@gmail.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21388559

Citation

Ali Ashfaq, Usman, et al. "Post-transcriptional Inhibition of Hepatitis C Virus Replication Through Small Interference RNA." Virology Journal, vol. 8, 2011, p. 112.
Ali Ashfaq U, Ansar M, Sarwar MT, et al. Post-transcriptional inhibition of hepatitis C virus replication through small interference RNA. Virol J. 2011;8:112.
Ali Ashfaq, U., Ansar, M., Sarwar, M. T., Javed, T., Rehman, S., & Riazuddin, S. (2011). Post-transcriptional inhibition of hepatitis C virus replication through small interference RNA. Virology Journal, 8, 112. https://doi.org/10.1186/1743-422X-8-112
Ali Ashfaq U, et al. Post-transcriptional Inhibition of Hepatitis C Virus Replication Through Small Interference RNA. Virol J. 2011 Mar 10;8:112. PubMed PMID: 21388559.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Post-transcriptional inhibition of hepatitis C virus replication through small interference RNA. AU - Ali Ashfaq,Usman, AU - Ansar,Muhammad, AU - Sarwar,Muhammad Tahir, AU - Javed,Tariq, AU - Rehman,Sidra, AU - Riazuddin,Sheikh, Y1 - 2011/03/10/ PY - 2011/02/22/received PY - 2011/03/10/accepted PY - 2011/3/11/entrez PY - 2011/3/11/pubmed PY - 2011/7/14/medline SP - 112 EP - 112 JF - Virology journal JO - Virol. J. VL - 8 N2 - BACKGROUND: Hepatitis C Virus (HCV) infection is a major health problem throughout world that causes acute and chronic infection which resulted in liver fibrosis, hepatocellular carcinoma and death. The only therapy currently available for HCV infection is the combination of pegylated interferon alpha (PEG-IFN α) and ribavirin. This therapy can effectively clear the virus infection in only 50% of infected individuals. Hence, there is a dire need to develop antiviral agents against HCV. RESULTS: This study was design to examine the ability of exogenous small interfering RNAs (siRNAs) to block the replication of HCV in human liver cells. In the present study six 21-bp siRNAs were designed against different regions of HCV non-structural genes (NS2, NS3 serine protease/helicase, NS4Band NS5B RNA dependent RNA polymerase). siRNAs were labeled as NS2si241, NS3si-229, NS3si-858, NS4Bsi-166, NS5Bsi-241 and NS5Bsi-1064. We found that siRNAs against HCV NS2- NS5B efficiently inhibit HCV replication in Huh-7 cells. Our results demonstrated that siRNAs directed against HCV NS3 (NS3si-229 and NS3si-858) showed 58% and 88% reduction in viral titer respectively. Moreover, NS4Bsi-166 and NS5Bsi-1064 exhibited a dramatic reduction in HCV viral RNA and resulted in greater than 90% inhibition at a 20 μM concentration, while NS2si-241 showed 27% reduction in viral titer. No significant inhibition was detected in cells transfected with the negative control siRNA. CONCLUSION: Our results suggest that siRNAs targeting against HCV non-structural genes (NS2-NS5B) efficiently inhibit HCV replication and combination of these siRNAs of different targets and interferon will be better option to treat HCV infection throughout the world. SN - 1743-422X UR - https://www.unboundmedicine.com/medline/citation/21388559/Post_transcriptional_inhibition_of_hepatitis_C_virus_replication_through_small_interference_RNA_ L2 - https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21388559/ DB - PRIME DP - Unbound Medicine ER -