Abstract
Hepatitis C virus (HCV) infection develops into chronic hepatitis in over two-thirds of acute infections. While current treatments with direct-acting antivirals (DAAs) achieve HCV eradication in >95% of cases, no vaccine is available and re-infection can readily occur. Natural killer (NK) cells represent a key cellular component of the innate immune system, participating in early defence against infectious diseases, viruses, and cancers. When acute infection becomes chronic, however, NK cell function is altered. This has been well studied in the context of HCV, where changes in frequency and distribution of NK cell populations have been reported. While activating receptors are downregulated on NK cells in both acute and chronic infection, NK cell inhibiting receptors are upregulated in chronic HCV infection, leading to altered NK cell responsiveness. Furthermore, chronic activation of NK cells following HCV infection contributes to liver inflammation and disease progression through enhanced cytotoxicity. Consequently, the NK immune response is a double-edged sword that is a significant component of the innate immune antiviral response, but persistent activation can drive tissue damage during chronic infection. This review will summarise the role of NK cells in HCV infection, and the changes that occur during HCV therapy.
Highlights
Hepatitis C virus (HCV) is a hepatotropic flavivirus and a major cause of chronic viral hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC) [1]
We have identified a population of KLRG1+ Natural killer (NK) cells that develop in response to chronic HCV infection: in response to HCV antigens (JFH1 infected Huh-7 cells) these memory NK cells undergo proliferation as well as degranulation that is absent in healthy controls
The innate immune system is an important player in antiviral immunity to HCV infection
Summary
Hepatitis C virus (HCV) is a hepatotropic flavivirus and a major cause of chronic viral hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC) [1]. Lower incidence is seen in the Oceania (0.1–1.5%), the Caribbean (0.2–1.3%), Europe (0.9–3.3%), and the Americas (0.9–1.9%) [4,5]. Despite these established ranges, countries such as Cameroon (13.8%), Burundi (11.3%), and Gabon (9.2%) have high HCV seroprevalence due to limited availability of HCV screening and treatment strategies [4,5]. While adaptive immunity and antigenic specificity of B and T cells to viral infection is generated through somatic rearrangement of antigenic receptors, it is significantly slower than the innate immune response. This review will focus on the role NK cells play in HCV infection, inflammation, and fibrosis, as well as their potential use as biomarkers for antiviral response and future treatment strategies
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