Inflammation is often a rapid coordinated response generated in the host against evading microbial infections or tissue injury. Microorganisms like bacteria and viruses instigate inflammation mediated by pro-inflammatory cytokines and activate cascade of signaling events leading to the recruitment of inflammatory cells (neutrophils and macrophages). Although the main function of inflammation is the resolution of infection, several viruses, including the hepatitis C viruses (HCV) have evolved to utilize this host response and make the cellular environments conducive to infection. In majority of infected individuals, HCV causes persistent chronic liver inflammation leading to development of liver cirrhosis and hepatocellular carcinoma. HCV induces reactive oxygen species (ROS) and activates nuclear factor-κB (NF-κB) leading to the activation of cyclooxygenase-2 (Cox-2) that ultimately produces prostaglandin-E2 (PGE2), thus enhancing inflammatory process. Interestingly, HCV further activates NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome (a multiprotein complex) by recruiting adaptor protein apoptosis-associated speck-like protein containing a carboxy-terminal CARD (ASC) which are involved in activation of caspase-1 leading to production of interleukin-1beta (IL-1β) and interleukin-18 (IL-18). In this chapter we have highlighted the recent advancements in HCV-induced inflammatory responses and discussed potential future directions to understand the role of inflammation during HCV infection.
Part of the book: Hepatitis C