title: Inhibition of hepatitis C virus using siRNA targeted to the virus and Hsp90.
abstract: 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.
authors.affiliation: Institute of Biosciences, Letters and Exact Sciences, UNESP, Rua Cristóvão Colombo, 2265, São José do Rio Preto, SP, CEP: 15054-000, Brazil.
authors.forename: Ana Claudia Silva
authors.initials: AC
authors.lastname: Braga
authors.affiliation: Institute of Biosciences, Letters and Exact Sciences, UNESP, Rua Cristóvão Colombo, 2265, São José do Rio Preto, SP, CEP: 15054-000, Brazil.|Institute of Exact and Natural Sciences, Mato Grosso Federal University, Rondonópolis, Brazil.
authors.forename: Bruno Moreira
authors.initials: BM
authors.lastname: Carneiro
authors.affiliation: Institute of Biosciences, Letters and Exact Sciences, UNESP, Rua Cristóvão Colombo, 2265, São José do Rio Preto, SP, CEP: 15054-000, Brazil.
authors.forename: Mariana Nogueira
authors.initials: MN
authors.lastname: Batista
authors.affiliation: Institute of Biosciences, Letters and Exact Sciences, UNESP, Rua Cristóvão Colombo, 2265, São José do Rio Preto, SP, CEP: 15054-000, Brazil.
authors.forename: Mônica Mayumi
authors.initials: MM
authors.lastname: Akinaga
authors.affiliation: Institute of Biosciences, Letters and Exact Sciences, UNESP, Rua Cristóvão Colombo, 2265, São José do Rio Preto, SP, CEP: 15054-000, Brazil. prahal@ibilce.unesp.br.
authors.forename: Paula
authors.initials: P
authors.lastname: Rahal
mesh_terms: D020121:5' Untranslated Regions; D045744:Cell Line, Tumor; D002470:Cell Survival; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D016174:Hepacivirus / Q000378:metabolism*; D006801:Humans; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism*; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; D012324:RNA-Dependent RNA Polymerase
chemical_list: D020121:5' Untranslated Regions; D018841:HSP90 Heat-Shock Proteins; D034741:RNA, Small Interfering; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase
keywords: HCV; Heat shock protein; Hepatitis C; Hsp90; RNA interference; siRNA