1. TGF‐β isoforms inhibit hepatitis C virus propagation in transforming growth factor beta/SMAD protein signalling pathway dependent and independent manners
- Author
-
Jian-Rui Li, Jia-Li Tan, Nan-Nan Liu, Hu Li, Li-Li Zou, Mei-Xi Wang, Xue‐Kai Wang, Haiyan Yan, Zong-Gen Peng, Biao Dong, Rong-Mei Gao, and Yu-Huan Li
- Subjects
Protein Conformation, alpha-Helical ,hepatitis C virus ,0301 basic medicine ,Gene isoform ,Hepatitis C virus ,Smad Proteins ,Hepacivirus ,SMAD ,Biology ,medicine.disease_cause ,Antiviral Agents ,Transforming Growth Factor beta1 ,Transforming Growth Factor beta2 ,addition ,TGF‐β isoform ,03 medical and health sciences ,Transforming Growth Factor beta3 ,0302 clinical medicine ,Transforming Growth Factor beta ,Viral entry ,Cell Line, Tumor ,medicine ,Humans ,Protein Isoforms ,Protein Interaction Domains and Motifs ,Amino Acid Sequence ,liver fibrosis ,TGF‐β signalling pathway ,Original Articles ,Cell Biology ,Transforming growth factor beta ,Virus Internalization ,Hepatitis C ,Hedgehog signaling pathway ,Cell biology ,030104 developmental biology ,Cell culture ,030220 oncology & carcinogenesis ,biology.protein ,RNA, Viral ,Molecular Medicine ,Original Article ,Signal Transduction ,Transforming growth factor - Abstract
Transforming growth factor beta (TGF‐β) plays an important role in the viral liver disease progression via controlling viral propagation and mediating inflammation‐associated responses. However, the antiviral activities and mechanisms of TGF‐β isoforms, including TGF‐β1, TGF‐β2 and TGF‐β3, remain unclear. Here, we demonstrated that all of the three TGF‐β isoforms were increased in Huh7.5 cells infected by hepatitis C virus (HCV), but in turn, the elevated TGF‐β isoforms could inhibit HCV propagation with different potency in infectious HCV cell culture system. TGF‐β isoforms suppressed HCV propagation through interrupting several different stages in the whole HCV life cycle, including virus entry and intracellular replication, in TGF‐β/SMAD signalling pathway–dependent and TGF‐β/SMAD signalling pathway–independent manners. TGF‐β isoforms showed additional anti‐HCV activities when combined with each other. However, the elevated TGF‐β1 and TGF‐β2, not TGF‐β3, could also induce liver fibrosis with a high expression of type I collagen alpha‐1 and α‐smooth muscle actin in LX‐2 cells. Our results showed a new insight into TGF‐β isoforms in the HCV‐related liver disease progression.
- Published
- 2021