Tgf-Beta Isoforms Inhibit Hepatitis C Virus Propagation In Transforming Growth Factor Beta/Smad Protein Signalling Pathway Dependent And Independent Manners

Transforming growth factor beta (TGF-beta) 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-beta isoforms, including TGF-beta 1, TGF-beta 2 and TGF-beta 3, remain unclear. Here, we demonstrated that all of the three TGF-beta isoforms were increased in Huh7.5 cells infected by hepatitis C virus (HCV), but in turn, the elevated TGF-beta isoforms could inhibit HCV propagation with different potency in infectious HCV cell culture system. TGF-beta isoforms suppressed HCV propagation through interrupting several different stages in the whole HCV life cycle, including virus entry and intracellular replication, in TGF-beta/SMAD signalling pathway-dependent and TGF-beta/SMAD signalling pathway-independent manners. TGF-beta isoforms showed additional anti-HCV activities when combined with each other. However, the elevated TGF-beta 1 and TGF-beta 2, not TGF-beta 3, could also induce liver fibrosis with a high expression of type I collagen alpha-1 and alpha-smooth muscle actin in LX-2 cells. Our results showed a new insight into TGF-beta isoforms in the HCV-related liver disease progression.