Figure 8.
Shown is a hypothetical model demonstrating how HCV-induced severe stress response impairs IFNAR1-p53-mediated innate antiviral loop that blocks transcription of type I IFN, ISGs, and IRFs. Low stress favors cellular p53-mediated cellular expression of ISGs and various IRFs that maintain the innate hepatic immunity and cellular apoptosis. Hepatic adaptive response to virus-associated stress selectively promotes CMA-associated degradation of IFNAR1, p53, and p14ARF and favors cell survival. Loss of IFNAR1 and p53 disables the activation of the innate feedback loop leading to severe impairment of innate immunity in the highly stressed cirrhotic liver.
