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Review
. 2013 Feb;48(2):169-76.
doi: 10.1007/s00535-012-0661-5. Epub 2012 Sep 11.

Role of miR-122 and lipid metabolism in HCV infection

Takasuke Fukuhara  1 , Yoshiharu Matsuura
Affiliations
Review

Role of miR-122 and lipid metabolism in HCV infection

Takasuke Fukuhara et al. J Gastroenterol. 2013 Feb.

Abstract

Hepatitis C virus (HCV) exhibits a narrow host range and a specific tissue tropism. Mice expressing major entry receptors for HCV permit viral entry, and therefore the species tropism of HCV infection is considered to be reliant on the expression of the entry receptors. However, HCV receptor candidates are expressed and replication of HCV-RNA can be detected in several nonhepatic cell lines, suggesting that nonhepatic cells are also susceptible to HCV infection. Recently it was shown that the exogenous expression of a liver-specific microRNA, miR-122, facilitated the efficient replication of HCV not only in hepatic cell lines, including Hep3B and HepG2 cells, but also in nonhepatic cell lines, including Hec1B and HEK-293T cells, suggesting that miR-122 is required for the efficient replication of HCV in cultured cells. However, no infectious particle was detected in the nonhepatic cell lines, in spite of the efficient replication of HCV-RNA. In the nonhepatic cells, only small numbers of lipid droplets and low levels of very-low-density lipoprotein-associated proteins were observed compared with findings in the hepatic cell lines, suggesting that functional lipid metabolism participates in the assembly of HCV. Taken together, these findings indicate that miR-122 and functional lipid metabolism are involved in the tissue tropism of HCV infection. In this review, we would like to focus on the role of miR-122 and lipid metabolism in the cell tropism of HCV.

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Figures

Fig. 1
Fig. 1
miR-122 enhances the translation of hepatitis C virus (HCV) RNA. Primary miRNA (pri-miRNA) transcribed by RNA polymerase II in the nucleus is processed into precursor miRNA (pre-miRNA) by Drosha and DiGeorge syndrome critical region protein 8 (DGCR8). Pre-miRNA is exported into the cytoplasm by nucleocytoplasmic shuttle protein exportin 5, processed to 22nt by dicer, and then incorporated into argonaute proteins to form the RNA-induced silencing complex (RISC). The passenger strand of miRNA (blue) is degraded and the guide strand (red) is matured in the RISC. Generally, miRNA represses the translation of host mRNA by binding to its 3’untranslated region (3′UTR). In contrast, liver-specific miR-122 binds to two sites in the 5′UTR of the HCV genome and enhances its translation and replication. GTP Guanosine-5-triphosphate, IRES internal ribosomal entry site
Fig. 2
Fig. 2
HCV replication in hepatocytes and nonhepatic cells. Chronic HCV infection induces liver cirrhosis and hepatocellular carcinoma (HCC), and is also often associated with the development of extrahepatic manifestations (EHM) such as malignant lymphoma and autoimmune diseases. Not only hepatocytes but also nonhepatic cells express major HCV receptors, including CD81, SR-BI, CLDN1, and OCLN. In hepatocytes, functional expression of miR-122 and lipid metabolism facilitate the efficient propagation of HCV. In contrast, the lack of expression of miR-122 and very-low-density lipoprotein (VLDL)-associated proteins might be associated with the incomplete propagation of HCV in nonhepatic cells. Low levels of HCV replication in nonhepatic cells may participate in the development of EHM
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