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World J Gastroenterol. Jun 21, 2014; 20(23): 7197-7206
Published online Jun 21, 2014. doi: 10.3748/wjg.v20.i23.7197
Regulation of microRNA by hepatitis B virus infection and their possible association with control of innate immunity
Xia Jiang, Tatsuo Kanda, Shuang Wu, Masato Nakamura, Tatsuo Miyamura, Shingo Nakamoto, Arup Banerjee, Osamu Yokosuka
Xia Jiang, Tatsuo Kanda, Shuang Wu, Masato Nakamura, Tatsuo Miyamura, Osamu Yokosuka, Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba 260-8677, Japan
Shingo Nakamoto, Department of Molecular Virology, Graduate School of Medicine, Chiba University, Chiba 260-8677, Japan
Arup Banerjee, Vaccine and Infectious Disease Research Center and Translational Health Science and Technology Institute, Gurgaon-122016, Haryana, India
Author contributions: Jiang X, Kanda T, Wu S, Nakamura M, Miyamura T, Nakamoto S, Banerjee A and Yokosuka O contributed to this paper.
Supported by Grants for “Asia-Oceania Collaborative Research Grants” from Kanae Foundation for the Promotion of Medical Science (to Kanda T); Grants for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology, Japan (to Kanda T)
Correspondence to: Tatsuo Kanda, MD, PhD, Associate Professor, Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan. kandat-cib@umin.ac.jp
Telephone: +81-43-2262086 Fax: +81-43-2262088
Received: October 17, 2013
Revised: December 11, 2013
Accepted: January 3, 2014
Published online: June 21, 2014
Processing time: 246 Days and 18 Hours
Abstract

Hepatitis B virus (HBV) chronically infects more than 350 million people worldwide. HBV causes acute and chronic hepatitis, and is one of the major causes of cirrhosis and hepatocellular carcinoma. There exist complex interactions between HBV and the immune system including adaptive and innate immunity. Toll-like receptors (TLRs) and TLR-signaling pathways are important parts of the innate immune response in HBV infections. It is well known that TLR-ligands could suppress HBV replication and that TLRs play important roles in anti-viral defense. Previous immunological studies demonstrated that HBV e antigen (HBeAg) is more efficient at eliciting T-cell tolerance, including production of specific cytokines IL-2 and interferon gamma, than HBV core antigen. HBeAg downregulates cytokine production in hepatocytes by the inhibition of MAPK or NF-κB activation through the interaction with receptor-interacting serine/threonine protein kinase. MicroRNAs (miRNAs) are also able to regulate various biological processes such as the innate immune response. When the expressions of approximately 1000 miRNAs were compared between human hepatoma cells HepG2 and HepG2.2.15, which could produce HBV virion that infects chimpanzees, using real-time RT-PCR, we observed several different expression levels in miRNAs related to TLRs. Although we and others have shown that HBV modulates the host immune response, several of the miRNAs seem to be involved in the TLR signaling pathways. The possibility that alteration of these miRNAs during HBV infection might play a critical role in innate immunity against HBV infection should be considered. This article is intended to comprehensively review the association between HBV and innate immunity, and to discuss the role of miRNAs in the innate immune response to HBV infection.

Keywords: Hepatitis B virus; HepG2.2.15; Innate immunity; MicroRNA; Persistent infection; Toll-like receptor

Core tip: Hepatitis B virus (HBV) is the leading cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma in the world. HBV could interact with the host’s innate and adaptive immune responses to establish chronic infection. HBV also interacts with Toll-like receptors (TLRs) and TLR signaling pathways, and regulates host immune responses through the regulation of microRNAs (miRNAs) to some extent. This article focuses on the involvement of miRNA in the association between HBV and TLR signaling pathways and reviews the miRNAs involved in HBV infection.