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http://dx.doi.org/10.14348/molcells.2021.0167

Hepatitis C Virus Nonstructural 5A Protein Interacts with Telomere Length Regulation Protein: Implications for Telomere Shortening in Patients Infected with HCV  

Lim, Yun-Sook (Laboratory of RNA Viral Diseases, Korea Zoonosis Research Institute, Jeonbuk National University)
Nguyen, Men T.N. (Ilsong Institute of Life Science, Hallym University)
Pham, Thuy X. (Laboratory of RNA Viral Diseases, Korea Zoonosis Research Institute, Jeonbuk National University)
Huynh, Trang T.X. (Laboratory of RNA Viral Diseases, Korea Zoonosis Research Institute, Jeonbuk National University)
Park, Eun-Mee (Center for Immunology and Pathology, National Institute of Health, Korea Center for Disease Control & Prevention)
Choi, Dong Hwa (Biocenter, Gyeonggido Business & Science Accelerator)
Kang, Sang Min (Laboratory for Infectious Disease Prevention, Korea Zoonosis Research Institute, Jeonbuk National University)
Tark, Dongseob (Laboratory for Infectious Disease Prevention, Korea Zoonosis Research Institute, Jeonbuk National University)
Hwang, Soon B. (Laboratory of RNA Viral Diseases, Korea Zoonosis Research Institute, Jeonbuk National University)
Publication Information
Molecules and Cells / v.45, no.3, 2022 , pp. 148-157 More about this Journal
Abstract
Hepatitis C virus (HCV) is a major cause of chronic liver disease and is highly dependent on cellular proteins for viral propagation. Using protein microarray analysis, we identified 90 cellular proteins as HCV nonstructural 5A (NS5A) interacting partners, and selected telomere length regulation protein (TEN1) for further study. TEN1 forms a heterotrimeric complex with CTC and STN1, which is essential for telomere protection and maintenance. Telomere length decreases in patients with active HCV, chronic liver disease, and hepatocellular carcinoma. However, the molecular mechanism of telomere length shortening in HCV-associated disease is largely unknown. In the present study, protein interactions between NS5A and TEN1 were confirmed by immunoprecipitation assays. Silencing of TEN1 reduced both viral RNA and protein expression levels of HCV, while ectopic expression of the siRNA-resistant TEN1 recovered the viral protein level, suggesting that TEN1 was specifically required for HCV propagation. Importantly, we found that TEN1 is re-localized from the nucleus to the cytoplasm in HCV-infected cells. These data suggest that HCV exploits TEN1 to promote viral propagation and that telomere protection is compromised in HCV-infected cells. Overall, our findings provide mechanistic insight into the telomere shortening in HCV-infected cells.
Keywords
hepatitis C virus; NS5A; protein microarray; telomere shortening; TEN1;
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