Antagonizing a killer: hepatitis C virus-infected cells inhibit natural killer cells

Holder, L. Kayla A. (2013) Antagonizing a killer: hepatitis C virus-infected cells inhibit natural killer cells. Masters thesis, Memorial University of Newfoundland.

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Abstract

Hepatitis C virus (HCV) infects at least 3% of the global population, 80% of those will develop chronic HCV infection, which can lead to liver scarring and hepatocellular carcinoma. Natural killer (NK) cells provide a rapid defense against viral infections, thus, evasion of NK cell functions may be key for the establishment of viral persistence and chronic infection. Here, we show that HCV-infected cells directly interact with, and dampen NK cell cytokine and cytotoxic functions, independent of cytopathic effects exerted by HCV infection of the human hepatoma cells. We observed no change in expression levels of NK cell activating receptors, NKG2D, NKp46 or CD16 on NK cells exposed to HCV infected cells, nor of human histocompatibility-linked leukocyte antigen (HLA)-E on HCV-infected compared to uninfected cells. However, surface expression of the natural cytotoxicity receptor NKp30 was reduced and infection of Huh-7.5 cells with HCV increased surface binding of an NKp30-lgG1 Fcγ fusion protein, suggesting up-regulation of an antagonistic NKp30 ligand on HCV-infected cells.

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