Journal of Microbial & Biochemical Technology

Exosomal miRNAs derived from umbilical mesenchymal stem cells inhibit hepatitis C virus infection

Joint Event on 4^th World Congress and Expo on Applied Microbiology & 2^nd International Conference on Food Microbiology

November 29-December 01, 2017 Madrid, Spain

Zhongtian Qi, Xijing Qian and Ping Zhao

Second Military Medical University, China

Scientific Tracks Abstracts: J Microb Biochem Technol

Abstract:

Background & Aim: Hepatitis C virus (HCV) infects approximately 3% of the world population. Though the development of directacting antivirals (DAAs) have improved the sustainable virological response (SVR) rate in HCV patients, novel anti-HCV agents with higher efficacy and better tolerance are still urgently needed. Cell-based therapy, like exosomes, has become one of the most popular therapeutic methods in recent years. Methods: Conditioned medium from umbilical mesenchymal stem cells (uMSC) is used to test its effect on HCV infection. Exosomes are further extracted and purified from the supernatants of uMSC (uMSC-Exo), and its anti-HCV activity is evaluated. Host cells are transfected with viral RNA or HCV replicon cells are utilized to detect the effect of uMSC-Exo on viral replication. Proteinase K treatment assay is used to determine which components in uMSC-Exo are the functional substances. Small RNA sequencing is made with uMSC-Exo, and miRNAs with antiviral potency are identified. Function analysis is carried out by overexpression or knockdown of relevant miRNAs, and their roles in inhibiting HCV infection are evaluated. Results: uMSC inhibit HCV infection by paracrine, and uMSC-Exo is the main active constituents in this process. uMSC-Exo can enter Huh7 cells and reduce intracellular HCV RNA level as well as viral protein expression in infected cells. uMSC-Exo have no effect on viral entry but suppress viral replication. Proteinase K treatment assay confirms that the RNA components are the active anti-HCV constituents in uMSC-Exo. Small RNA sequencing of uMSC-Exo indicates their miRNA expression profile. Among them, nine miRNAs are upregulated in the host cells after uMSC-Exo treatment. The functional analysis suggests four miRNAs (let-7f, miR-145, miR-199a, and miR-221) play important roles in HCV infection. The inhibitory effect of uMSC-Exo is lost when the uMSC are transfected with the inhibitors of the four miRNAs.uMSC-Exo exhibit synergistic effect when combined with IFN or VX-950. Conclusion: uMSC-Exo inhibits HCV infection by exosomal miRNAs (let-7f, miR-145, miR-199a, and miR-221) with antiviral activity on viral replication. This work provides novel insights and the possibility of developing an anti-HCV therapy.

Biography :

Zhongtian Qi has completed his MD from Second Military Medical University, China and Postdoctoral studies from New York University School of Medicine. He has been working on Clinical Microbiology for more than ten years, and has published more than 75 papers in reputed journals.