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World J Gastroenterol. Dec 21, 2013; 19(47): 8902-8909
Published online Dec 21, 2013. doi: 10.3748/wjg.v19.i47.8902
Exploitation of host clock gene machinery by hepatitis viruses B and C
Manlio Vinciguerra, Gianluigi Mazzoccoli, Claudia Piccoli, Tiziana Tataranni, Angelo Andriulli, Valerio Pazienza
Manlio Vinciguerra, Institute for Liver and Digestive Health, Division of Medicine, University College London (UCL), London SW7 2AZ, United Kingdom
Manlio Vinciguerra, Angelo Andriulli, Valerio Pazienza, Gastroenterology Unit, IRCCS “Casa Sollievo della Sofferenza” Hospital, 71013 San Giovanni Rotondo (FG), Italy
Gianluigi Mazzoccoli, Department of Medical Sciences, Division of Internal Medicine, IRCCS Scientific Institute and Regional General Hospital “Casa Sollievo della Sofferenza”, 71013 San Giovanni Rotondo (FG), Italy
Claudia Piccoli, Department of Clinical and Experimental Medicine, University of Foggia, 71100 Foggia, Italy
Claudia Piccoli, Tiziana Tataranni, Laboratory of Pre-Clinical and Translational Research, IRCCS, Centro di Riferimento Oncologico della Basilicata (CROB), 85028 Rionero in Vulture (PZ), Italy
Author contributions: Pazienza V conceived, designed and wrote the manuscript; Vinciguerra M drafted the manuscript; Mazzoccoli G, Piccoli C, Tataranni T and Andriulli A helped in drafting the manuscript.
Supported by RC1303GA49 and Italian Ministry of Health (Pazienza V); MV and VP are supported by Bando GR-2010-2311017 and by the “5x1000” voluntary contributions to IRCCS “Casa Sollievo della Sofferenza” Hospital (Vinciguerra M and Pazienza V); and the Associazione Italiana per la Ricerca sul Cancro (AIRC) program MyFAG (Vinciguerra M)
Correspondence to: Dr. Valerio Pazienza, Gastroenterology Unit, IRCCS “Casa Sollievo della Sofferenza” Hospital, Viale Cappuccini 1, 71013 San Giovanni Rotondo (FG), Italy.
Telephone: +39-88-2416281 Fax: +39-88-2416271
Received: August 28, 2013
Revised: October 30, 2013
Accepted: November 18, 2013
Published online: December 21, 2013

Many aspects of cellular physiology display circadian (approximately 24-h) rhythms. Dysfunction of the circadian clock molecular circuitry is associated with human health derangements, including neurodegeneration, increased risk of cancer, cardiovascular diseases and the metabolic syndrome. Viruses triggering hepatitis depend tightly on the host cell synthesis machinery for their own replication, survival and spreading. Recent evidences support a link between the circadian clock circuitry and viruses’ biological cycle within host cells. Currently, in vitro models for chronobiological studies of cells infected with viruses need to be implemented. The establishment of such in vitro models would be helpful to better understand the link between the clock gene machinery and viral replication/viral persistence in order to develop specifically targeted therapeutic regimens. Here we review the recent literature dealing with the interplay between hepatitis B and C viruses and clock genes.

Keywords: Hepatitis C virus, Hepatitis B virus, Anti-hepatitis therapy, Clock genes, Chronobiology

Core tip: New antiviral strategies have been developed, including the interferon/ribavirin-free therapy, to control hepatitis viruses replication. Although, IFN-free regimens have generated excitement among scientists, for the reason that they are better tolerated, they are not still able to completely eradicate the viruses. Here we underline the circadian relationship between host cell and hosted hepatitis viruses, that has to be taken into account in order to optimize the timing of therapeutic regimens, not only to minimize the pharmacological agents’ toxicity but also to improve the efficacy of treatment modalities through optimized timing of therapeutic regimens, targeting in a better way virus replication.