Despite the availability of antiviral treatments, Hepatitis C virus (HCV) persists
a considerable risk factor for the development of chronic liver diseases and hepatocellular
carcinoma (HCC). Previous work from our research group indicates that HCV reprograms
intercellular communication in the host by modulating the expression of growth factors.
Furthermore, we have observed that patients with HCV infection exhibit elevated plasma
levels of IL-1β, independent of viral eradication. This suggests that HCV induces
persistent modifications in host cellular functions, which contribute to liver disease
progression. Therefore, this study aims to investigate the impact of HCV on the host
cellular response to IL-1β.
Human hepatoma cell line harboring the HCV genotype 1b subgenomic replicon (Huh9-13)
and Huh7 controls, were treated with IL-1β. Subsequently, we assessed the levels of
IL-1β target protein IκBα using western blot analysis. Additionally, the phosphorylation
profile of IκBα (Ser32/36) was evaluated. Next, Huh7.5 cells infected with the strain
JC1 (HCVcc) were used to further investigate the effects of chronic HCV infection
on IκBα signaling.
Our findings indicate that HCV reduces basal IκBα protein levels and impairs its recovery
following IL-1β stimulation in both the replicon and chronic infection systems. Notably,
the phosphorylation profile analysis revealed that Huh9-13 cells exhibit an accelerated
rate of IκBα phosphorylation, and degradation, as well as a reduced recovery after
120 minutes compared to the control.
Conclusively, HCV alters IL-1β-induced signaling through modulation of IκBα, leading
to enhanced expression of NFκB-regulated genes and subsequent alterations in the host
immune response to HCV.
