RNA Interference Effectively Inhibits mRNA Accumulation and Protein Expression of Hepatitis C Virus Core and E2 Genes in Human Cells

Liu, Min; Zhao, Ping; Qin, Zhao-ling; Gao, Jun; Cao, Ming-Mei; Luan, Jie; Wu, Wen‐Bin; Qi, Zhongtian

doi:10.1271/bbb.60001

Cited by 28 publications

(23 citation statements)

References 38 publications

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“…Although highly variable regions are poor targets of gene silencing, the results indicate that it is possible to target siRNAs at the conserved regions within the variable envelope region for obtaining a moderate anti-BVDV-1 effect. Our results also get support from an earlier study showing efficient inhibition of hepatitis C virus in human cells by siRNA targeting the E2 envelope region (Liu et al, 2006). Although the causes of non-inhibitory effect of si1921(E1) have not been ascertained, the possible reasons include inaccessibility of the target RNA region to the RNA-induced silencing complex (RISC) or inability of siRNA to form RISC essential for gene silencing.…”

Section: Discussionsupporting

confidence: 86%

Small interfering RNAs targeting viral structural envelope protein genes and the 5ʹ-UTR inhibit replication of bovine viral diarrhea virus in MDBK cells

Mishra¹,

Rajukumar²,

Kalaiyarasu³

et al. 2011

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Summary. -Bovine viral diarrhea viruses (BVDVs) are important pathogens of cattle that occur worldwide, and for which no antiviral therapy is available. In the present study, the inhibitory effect of small interfering (si) RNAs on bovine viral diarrhea virus 1 (BVDV-1) replication in cultured bovine cells was explored. Four synthetic siRNAs were designed to target structural envelope region genes (E rns , E1, and E2) and one cocktail of siRNA was generated to target the 5ʹ-UTR of the BVDV-1 genome. The inhibitory effects of siRNAs were assessed by determination of infectious viral titer, viral antigen and viral RNA. The siRNA cocktail and three of the synthetic siRNAs produced moderate anti-BVDV-1 effect in vitro as shown by 25%-40% reduction in BVDV-1 antigen production, 7.9-19.9-fold reduction in viral titer and 21-48-fold reduction in BVDV-1 RNA copy number. Our findings suggest that siRNA cocktail targeted at the 5ʹ-UTR is a stronger inhibitor of BVDV-1 replication and the targets for siRNA inhibition can be extended to BVDV-1 structural envelope protein genes.Keywords: bovine viral diarrhea virus; RNA interference; small interfering RNA E-mail: mishranir@rediffmail.com; fax: +91-755-2758842. Abbreviations: BVDVs = bovine viral diarrhea viruses; BVDV-1 = bovine viral diarrhea virus 1; BVDV-2 = bovine viral diarrhea virus 2; siRNA = small interfering RNA; IRES = internal ribosome entry site; CSFV = classical swine fever virus; HCV = hepatitis C virus; MAb = monoclonal antibody; p.i. = post infection

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Section: Discussionsupporting

confidence: 86%

Small interfering RNAs targeting viral structural envelope protein genes and the 5ʹ-UTR inhibit replication of bovine viral diarrhea virus in MDBK cells

Mishra¹,

Rajukumar²,

Kalaiyarasu³

et al. 2011

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“…Moreover, decrease of NS4 protein expression was observed when both Vero E6-shRNA-E and Vero E6-shRNA-NS1 were challenged with YFV. Other studies have demonstrated the effectiveness of RNAi in the inhibition of Flavivirus replication using NS1 and envelope genes as targets [23,24,32].…”

Section: Discussionmentioning

confidence: 99%

RNA interference inhibits yellow fever virus replication in vitro and in vivo

et al. 2009

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RNA interference (RNAi) is a process that is induced by double stranded RNA and involves the degradation of specific sequences of mRNA in the cytoplasm of the eukaryotic cells. It has been used as an antiviral tool against many viruses, including flaviviruses. The genus Flavivirus contains the most important arboviruses in the world, i.e., dengue (DENV) and yellow fever (YFV). In our study, we investigated the in vitro and in vivo effect of RNAi against YFV. Using stable cell lines that expressed RNAi against YFV, the cell lines were able to inhibit as much as 97% of the viral replication. Two constructions (one against NS1 and the other against E region of YFV genome) were able to protect the adult Balb/c mice against YFV challenge. The histopathologic analysis demonstrated an important protection of the central nervous system by RNAi after 10 days of viral challenge. Our data suggests that RNAi is a potential viable therapeutic weapon against yellow fever.

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“…Target RNA cleavage or translation inhibition 5'-UTR and 3'-UTR [93][94][95][96][100][101][102] Protein coding regions [103][104][105][106][107][108][109] Antisense oligonucleotide Bind to complementary RNAs and suppress the access to cellular machinery, thereby inhibiting expression or function of the targeted RNAs 5'-UTR [134][135][136][137] Completion of Phase Ⅱ…”

Section: Rnaimentioning

confidence: 99%

“…A number of groups have demonstrated siRNAs or shRNAs that target the protein coding regions of HCV. Three different groups have shown that siRNA against the HCV core region reduced HCV RNA and protein expression [103][104][105][106] . Ansar et al [106] showed that siRNAs against the HCV core region showed a 70% reduction in viral titers, while siRNAs against E1 and E2 caused viral titers to drop by as much as 93% in HCV-infected liver cells.…”

Section: Rnai Against Hcv Coding Regionsmentioning

confidence: 99%

Prospects for nucleic acid-based therapeutics against hepatitis C virus

Lee

Kim

Lee

2013

WJG

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In this review, we discuss recent advances in nucleic acid-based therapeutic technologies that target hepatitis C virus (HCV) infection. Because the HCV genome is present exclusively in RNA form during replication, various nucleic acid-based therapeutic approaches targeting the HCV genome, such as ribozymes, aptamers, siRNAs, and antisense oligonucleotides, have been suggested as potential tools against HCV. Nucleic acids are potentially immunogenic and typically require a delivery tool to be utilized as therapeutics. These limitations have hampered the clinical development of nucleic acid-based therapeutics. However, despite these limitations, nucleic acid-based therapeutics has clinical value due to their great specificity, easy and large-scale synthesis with chemical methods, and pharmaceutical flexibility. Moreover, nucleic acid therapeutics are expected to broaden the range of targetable molecules essential for the HCV replication cycle, and therefore they may prove to be more effective than existing therapeutics, such as interferon-α and ribavirin combination therapy. This review focuses on the current status and future prospects of ribozymes, aptamers, siRNAs, and antisense oligonucleotides as therapeutic reagents against HCV.

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RNA Interference Effectively Inhibits mRNA Accumulation and Protein Expression of Hepatitis C Virus Core and E2 Genes in Human Cells

Cited by 28 publications

References 38 publications

Small interfering RNAs targeting viral structural envelope protein genes and the 5ʹ-UTR inhibit replication of bovine viral diarrhea virus in MDBK cells

Small interfering RNAs targeting viral structural envelope protein genes and the 5ʹ-UTR inhibit replication of bovine viral diarrhea virus in MDBK cells

RNA interference inhibits yellow fever virus replication in vitro and in vivo

Prospects for nucleic acid-based therapeutics against hepatitis C virus

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