Mechanistic study of interaction between IL-22 and HCV core protein in the development of hepatocellular carcinoma among liver transplant recipients.

BACKGROUND

Hepatitis C virus (HCV) infects more than 170 million people worldwide that represents a major threat to global public health. Several viruses including HCV have developed mechanisms against the cellular responses essentially "hijacking" the antiviral responses generated against it. Interleukin 22 activated JAK-STAT pathways are responsible for several functions including liver regeneration, antiviral responses and cell cycle regulation.

OBJECTIVES

Present study aims to un-reveal the speculated role of HCV core protein in perturbing IL-22 mediated JAK-STAT pathway. Principally investigating through interaction with IL-22 and SOCS-3 proteins.

PATIENTS AND METHODOLOGY

Total 36 liver transplant patients were enrolled in the study. Out of which 24 were found HCV + ve. Immunohistochemistry (IHC) based qualitative expression analysis of IL-22, SOCS-3 and HCV core protein was carried out. Microscopy was performed for detection and visualization of immunostained liver tissues and biopsies.

RESULTS

Hepatic expression of IL-22, HCV core protein and SOCS-3 showed that SOCS-3 expression levels were considerably high compared to HCV core and IL-22 protein. IL-22's moderate to high expression was found in 70% of the liver transplant patient sample. Total 87% patients showed moderate to high SOCS-3 expression. However, the overall expression of HCV core was stronger in 87% of cirrhotic patients and 14% in HCC patients. Suggesting the presence of HCV core protein clearly impacted the IL-22 mediated cellular signaling (JAK-STAT pathway leading towards hepatocarcinogenesis.

CONCLUSION

HCV core and IL-22 and SOCS-3 molecules are found to be correlated statistically under this study. Concluded from this study that HCV core protein plays a potential role in diverging the hepatocytes from normal to carcinogenic. One cell signaling path cannot decide, the direct role of a single viral protein in developing viral induced hepatocarcinogenesis. Interpreting the complex network of cell signaling involved in HCC development is impractical to study under single study. That is why step by step unmasking the interactive role of few molecules under single study is the ideal way to resolve the impact of viral proteins on cell signaling. SOCS-3 is mediator for dysregulating IL-22 mediated liver regenerative pathway. Moreover, SOCS-3 and STAT-3 molecules are proposed to be a potential therapeutic target for managing HCC progression.