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World J Gastroenterol. Mar 21, 2014; 20(11): 2913-2926
Published online Mar 21, 2014. doi: 10.3748/wjg.v20.i11.2913
Understanding the interaction of hepatitis C virus with host DEAD-box RNA helicases
Megha Haridas Upadya, Jude Juventus Aweya, Yee-Joo Tan
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
Yee-Joo Tan, Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore 138673, Singapore
Author contributions: Tan YJ designed the research; Upadya MH performed the research; Upadya MH, Aweya JJ and Tan YJ co-wrote the manuscript; all authors read and approved the final version of the manuscript.
Supported by Grants from the Ministry of Education of Singapore, Academic Research Fund Tier 1 Grant R-182-000-170-112
Correspondence to: Yee-Joo Tan, Associate Professor, Department of Microbiology, Yong Loo Lin School of Medicine, National University Health System (NUHS), National University of Singapore, MD4A, 5 Science Drive 2, Singapore 117597, Singapore. yee_joo_tan@nuhs.edu.sg
Telephone: +65-651-63692 Fax: +65-677-66872
Received: September 27, 2013
Revised: December 6, 2013
Accepted: January 19, 2014
Published online: March 21, 2014
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.

Keywords: Hepatitis C virus, Chronic hepatitis C, Hepatitis C virus therapy, DEAD-box helicases, Host factors, Hepatocellular carcinoma

Core tip: Alternative treatments to combat chronic hepatitis C include direct-acting antivirals targeting hepatitis C virus (HCV) enzymes and host targeting agents that interfere with host factors essential for the viral life cycle. Several members of a family of host proteins known as DEAD-box RNA helicases have been shown to modulate HCV replication. This review highlights their interaction with HCV and their role in viral replication. Since hepatocellular carcinoma (HCC) is a major cause of death among patients with chronic hepatitis C, the involvement of these DEAD-box RNA helicases in the development of HCC will also be discussed.