The reduction of miR146b-5p in monocytes and T cells could contribute to the immunopathogenesis of hepatitis C virus infection

• Published in: Scientific reports Vol. 9; no. 1; pp. 13393 - 13
• Main Authors: Kondo, Yasuteru, Kogure, Takayuki, Ninomiya, Masashi, Fukuda, Ryo, Monma, Norikazu, Ikeo, Kazuho, Tanaka, Yasuhito
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 16.09.2019; Nature Publishing Group
• Subjects: 38; 38/109; 38/47; 38/77; 692/4020/4021/1607/1610/4029; 692/4020/4021/1607/234/2513/1551; Case-Control Studies; CD14 antigen; CD3 antigen; Cytokines; Gene Expression Profiling; Hepacivirus - immunology; Hepatitis; Hepatitis C; Hepatitis C - genetics; Hepatitis C - immunology; Hepatitis C - pathology; Hepatitis C - virology; Humanities and Social Sciences; Humans; Immunopathogenesis; Infections; Interferon; Lymphocytes; Lymphocytes T; MicroRNAs - genetics; Monocytes; Monocytes - immunology; Monocytes - metabolism; Monocytes - pathology; Monocytes - virology; multidisciplinary; NF-κB protein; Patients; Science; Science (multidisciplinary); T-Lymphocytes - immunology; T-Lymphocytes - metabolism; T-Lymphocytes - pathology; T-Lymphocytes - virology; Vitamin D3
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-49706-9

It has been reported that various kinds of miRNAs could affect the pathogenesis of hepatitis C virus infection. Recently, our group reported that deep-sequencing analysis was useful to detect disease-specific miRNAs. The aim of this study is to identify the HCV-specific miRNAs that could contribute to the immunopathogenesis of HCV by using clinical samples and in vitro analysis. Five miRNAs (hsa-miR181a-2-3p, hsa-miR-374a-3p, hsa-miR374a-5p, hsa-miR-204-5p and hsa-miR146b-5p) were shown to be significantly downregulated in CH-C by deep sequence analysis. The average ratio (PBMCs miRNAs/serum miRNAs) of hsa-miR146b-5p was highest among all the miRNAs. Moreover, serum hsa-miR146b-5p was significantly down-regulated in CH-C patients in comparison to CH-B patients and healthy subjects. The expression of hsa-miR146b-5p in CD3 + T cells and CD14 + monocytes of CH-C patients was significantly lower than that of the other groups. The hsa-miR146b-5p expression in CD14 + monocytes of SVR patients treated with Peg-IFN/RBV was significantly higher than in those of non-SVR patients treated with Peg IFN/RBV. However, the hsa-miR146b-5p expression in CD14 + monocytes of SVR patients treated with DCV and ASV was comparable to that in monocytes of non-SVR patients treated with DCV and ASV. Moreover, the expression levels of hsa-miR146b-5p in CD14 + monocytes were significantly increased after achieving SVR and 1(OH)Vitamin D3 treatment. Further, the expression of HCV-Core could suppress miR146b-5p expression in immune cells and affect the expression of various kinds of cytokines by affecting the NF-κB signaling. In conclusion, the reduction of miR146b-5p in monocytes and T cells could contribute to the immunopathogenesis of hepatitis C virus infection.