丙型肝炎病毒 z-bo 2020-08-31 451

　　The Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences has made new progress in the research on the pathogenicity and infectivity of hepatitis C virus, and the relevant research results have been published online in the Journal of Virology. According to the latest WHO statistics, currently about 185 million people worldwide are chronically infected with hepatitis C virus (HCV); the carrier rate of hepatitis C virus in my country is as high as 3.5%, and the incidence rate is increasing year by year. HCV infection can not only cause liver diseases such as chronic hepatitis, fatty liver, cirrhosis, and liver cancer, but also metabolic diseases (such as insulin resistance and type 2 diabetes). The mechanism of HCV infection to replicate itself and cause metabolic diseases remains to be studied in depth. The Peng Tao Laboratory of Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences found that HCV infection simultaneously up-regulated the expression of WT-PGC-1α and L-PGC-1α. The up-regulated PGC-1α promotes the production of HCV virus on the one hand, and causes HCV on the other hand. Induced insulin resistance; the upregulation of PGC-1α by HCV infection depends on HCV RNA replication, and ER stress mediates this upregulation.

　　PGC-1α acts as a co-activator and realizes the transcriptional regulation of downstream target genes through interaction with other transcription factors. As a key regulator of energy metabolism, PGC-1α participates in the regulation of gluconeogenesis and fatty acid oxidation in the liver. In 2011, it was reported that a new isomer of PGC-1α in the human liver was discovered, namely L-PGC-1α; correspondingly, the previous classic PGC-1α was called WT-PGC-1α. The results of Peng Tao's laboratory showed that HCV infection can up-regulate the expression of the above two forms of PGC-1α. ER stress mediates the up-regulation of PGC-1α by HCV infection; the results also show that ER stress inhibitor PBA can inhibit HCV infection While up-regulating PGC-1α, it can also inhibit the production of HCV virus (PBA has been approved by the US FDA for the treatment of abnormal urea cycle). The research results not only deepen people's understanding of HCV pathogenicity and infectivity in mechanism, but also suggest that HCV-ERstress-PGC-1α signaling pathway can be used as a potential drug target for the treatment of HCV infection and related insulin resistance.