title: Understanding the interaction of hepatitis C virus with host DEAD-box RNA helicases.
abstract: The current therapeutic regimen to combat chronic hepatitis C is not optimal due to substantial side effects and the failure of a significant proportion of patients to achieve a sustained virological response. Recently developed direct-acting antivirals targeting hepatitis C virus (HCV) enzymes reportedly increase the virologic response to therapy but may lead to a selection of drug-resistant variants. Besides direct-acting antivirals, another promising class of HCV drugs in development include host targeting agents that are responsible for interfering with the host factors crucial for the viral life cycle. A family of host proteins known as DEAD-box RNA helicases, characterized by nine conserved motifs, is known to play an important role in RNA metabolism. Several members of this family such as DDX3, DDX5 and DDX6 have been shown to play a role in HCV replication and this review will summarize our current knowledge on their interaction with HCV. As chronic hepatitis C is one of the leading causes of hepatocellular carcinoma, the involvement of DEAD-box RNA helicases in the development of HCC will also be highlighted. Continuing research on the interaction of host DEAD-box proteins with HCV and the contribution to viral replication and pathogenesis could be the panacea for the development of novel therapeutics against HCV.
authors.affiliation: Megha Haridas Upadya, Jude Juventus Aweya, Yee-Joo Tan, Department of Microbiology, Yong Loo Lin School of Medicine, National University Health System (NUHS), National University of Singapore, Singapore 117597, Singapore.
authors.forename: Megha Haridas
authors.initials: MH
authors.lastname: Upadya
authors.affiliation: Megha Haridas Upadya, Jude Juventus Aweya, Yee-Joo Tan, Department of Microbiology, Yong Loo Lin School of Medicine, National University Health System (NUHS), National University of Singapore, Singapore 117597, Singapore.
authors.forename: Jude Juventus
authors.initials: JJ
authors.lastname: Aweya
authors.affiliation: Megha Haridas Upadya, Jude Juventus Aweya, Yee-Joo Tan, Department of Microbiology, Yong Loo Lin School of Medicine, National University Health System (NUHS), National University of Singapore, Singapore 117597, Singapore.
authors.forename: Yee-Joo
authors.initials: YJ
authors.lastname: Tan
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000209:etiology; D053487:DEAD-box RNA Helicases / Q000378:metabolism*; D016679:Genome, Viral; D016174:Hepacivirus / Q000502:physiology*; D006526:Hepatitis C / Q000188:drug therapy / Q000201:enzymology*; D054884:Host-Pathogen Interactions; D006801:Humans; D008113:Liver Neoplasms / Q000209:etiology; D014764:Viral Proteins / Q000378:metabolism
chemical_list: D000998:Antiviral Agents; D014764:Viral Proteins; D053487:DEAD-box RNA Helicases
keywords: Chronic hepatitis C; DEAD-box helicases; Hepatitis C virus; Hepatitis C virus therapy; Hepatocellular carcinoma; Host factors