Abstract
More than 170 million individuals worldwide are infected by hepatitis C virus (HCV) and it is one of the most common etiologic agents of chronic liver diseases, including liver cirrhosis and hepatocellular carcinoma. Current standard therapy combining peg-interferon, ribavirin, and a protease inhibitor has achieved a sustained virologic response in more than 80 % of individuals infected with HCV. In addition, other directly acting antivirals (DAAs) targeting to the viral non-structural proteins, including NS3, NS5A and NS5B, have been gradually applied in clinical settings. Recent reports have shown that combination therapy using different types of DAAs further improves the outcomes. However, previous reports have shown that drug-resistant variants can emerge during treatment with DAAs. In addition, most patients in developing countries are not able to access or afford such advanced therapies. Furthermore, it remains unclear whether elimination of HCV by DAAs can protect against HCV-induced liver diseases. In this review, we summarize our current data regarding molecular mechanisms of HCV-induced liver diseases.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Galossi A, Guarisco R, Bellis L et al (2007) Extrahepatic manifestations of chronic HCV infection. J Gastrointestin Liver Dis 16(1):65–73
Hüssy P, Langen H, Mous J et al (1996) Hepatitis C virus core protein: carboxy-terminal boundaries of two processed species suggest cleavage by a signal peptide peptidase. Virology 224(1):93–104
Li Y, Tang ZY, Hou JX (2011) Hepatocellular carcinoma: insight from animal models. Nat Rev Gastroenterol Hepatol 9(1):32–43
Maasoumy B, Wedemeyer H (2012) Natural history of acute and chronic hepatitis C. Best Pract Res Clin Gastroenterol 26(4):401–412
McLauchlan J, Lemberg MK, Hope G et al (2002) Intramembrane proteolysis promotes trafficking of hepatitis C virus core protein to lipid droplets. EMBO J 21(15):3980–3988
Miyamoto H, Moriishi K, Moriya K et al (2007) Involvement of the PA28γ-dependent pathway in insulin resistance induced by hepatitis C virus core protein. J Virol 81(4):1727–1735
Moradpour D, Penin F, Rice CM (2007) Replication of hepatitis C virus. Nat Rev Microbiol 5(6):453–463
Mori Y, Moriishi K, Matsuura Y (2008) Hepatitis C virus core protein: Its coordinate roles with PA28γ in metabolic abnormality and carcinogenicity in the liver. Int J Biochem Cell Biol 40(8):1437–1442
Moriishi K, Matsuura Y (2003) Mechanisms of hepatitis C virus infection. Antiviral Chem Chemother 14(6):285–297
Moriishi K, Okabayashi T, Nakai K et al (2003) Proteasome activator PA28γ-dependent nuclear retention and degradation of hepatitis C virus core protein. J Virol 77(19):10237–10249
Moriishi K, Mochizuki R, Moriya K et al (2007) Critical role of PA28γ in hepatitis C virus-associated steatogenesis and hepatocarcinogenesis. Proc Natl Acad Sci U S A 104(5):1661–1666
Moriya K, Fujie H, Shintani Y et al (1998) The core protein of hepatitis C virus induces hepatocellular carcinoma in transgenic mice. Nat Med 4(9):1065–1067
Okamoto K, Moriishi K, Miyamura T et al (2004) Intramembrane proteolysis and endoplasmic reticulum retention of hepatitis C virus core protein. J Virol 78(12):6370–6380
Okamoto K, Mori Y, Komoda Y et al (2008) Intramembrane processing by signal peptide peptidase regulates the membrane localization of hepatitis C virus core protein and viral propagation. J Virol 82(17):8349–8361
Shintani Y, Fujie H, Miyoshi H et al (2004) Hepatitis C virus infection and diabetes: direct involvement of the virus in the development of insulin resistance. Gastroenterology 126(3):840–848
Suzuki R, Moriishi K, Fukuda K et al (2009) Proteasomal turnover of hepatitis C virus core protein is regulated by two distinct mechanisms: a ubiquitin-dependent mechanism and a ubiquitin-independent but PA28γ-dependent mechanism. J Virol 83(5):2389–2392
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2015 Springer Japan
About this chapter
Cite this chapter
Okamoto, T., Matsuura, Y. (2015). Host Factors Involved in the Propagation and Pathogenesis of Hepatitis C Virus. In: Seya, T., Matsumoto, M., Udaka, K., Sato, N. (eds) Inflammation and Immunity in Cancer. Springer, Tokyo. https://doi.org/10.1007/978-4-431-55327-4_8
Download citation
DOI: https://doi.org/10.1007/978-4-431-55327-4_8
Publisher Name: Springer, Tokyo
Print ISBN: 978-4-431-55326-7
Online ISBN: 978-4-431-55327-4
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)