Article

Expression of microRNA miR-122 facilitates an efficient replication in nonhepatic cells upon infection with hepatitis C virus.

Department of Molecular Virology, Osaka University, Osaka, Japan.
Journal of Virology (impact factor: 5.4). 05/2012; 86(15):7918-33. DOI:10.1128/JVI.00567-12
Source: PubMed

ABSTRACT Hepatitis C virus (HCV) is one of the most common etiologic agents of chronic liver diseases, including liver cirrhosis and hepatocellular carcinoma. In addition, HCV infection is often associated with extrahepatic manifestations (EHM), including mixed cryoglobulinemia and non-Hodgkin's lymphoma. However, the mechanisms of cell tropism of HCV and HCV-induced EHM remain elusive, because in vitro propagation of HCV has been limited in the combination of cell culture-adapted HCV (HCVcc) and several hepatic cell lines. Recently, a liver-specific microRNA called miR-122 was shown to facilitate the efficient propagation of HCVcc in several hepatic cell lines. In this study, we evaluated the importance of miR-122 on the replication of HCV in nonhepatic cells. Among the nonhepatic cell lines expressing functional HCV entry receptors, Hec1B cells derived from human uterus exhibited a low level of replication of the HCV genome upon infection with HCVcc. Exogenous expression of miR-122 in several cells facilitates efficient viral replication but not production of infectious particles, probably due to the lack of hepatocytic lipid metabolism. Furthermore, expression of mutant miR-122 carrying a substitution in a seed domain was required for efficient replication of mutant HCVcc carrying complementary substitutions in miR-122-binding sites, suggesting that specific interaction between miR-122 and HCV RNA is essential for the enhancement of viral replication. In conclusion, although miR-122 facilitates efficient viral replication in nonhepatic cells, factors other than miR-122, which are most likely specific to hepatocytes, are required for HCV assembly.

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Keywords

cell culture-adapted HCV
 
common etiologic agents
 
efficient propagation
 
Exogenous expression
 
HCV assembly
 
HCV genome
 
HCV infection
 
HCV RNA
 
HCV-induced EHM
 
Hec1B cells
 
hepatic cell lines
 
likely specific
 
liver-specific microRNA
 
mixed cryoglobulinemia
 
mutant HCVcc
 
mutant miR-122
 
non-Hodgkin's lymphoma
 
nonhepatic cell lines
 
nonhepatic cells
 
vitro propagation
 

Takasuke Fukuhara