Immunomodulation of the Natural Killer Cell Phenotype and Response during HCV Infection

Gaitan Fabrice Njiomegnie; Scott A Read; Nicole Fewings; Jacob George; Fiona McKay; Golo Ahlenstiel

doi:10.3390/jcm9041030

Immunomodulation of the Natural Killer Cell Phenotype and Response during HCV Infection

J Clin Med. 2020 Apr 6;9(4):1030. doi: 10.3390/jcm9041030.

Authors

Gaitan Fabrice Njiomegnie^{1

2}, Scott A Read^{1

2

3}, Nicole Fewings^{4

5}, Jacob George^{1

2

5

6}, Fiona McKay^{4

5}, Golo Ahlenstiel^{1

2

3

5}

Affiliations

¹ Blacktown Clinical School and Research Centre, Western Sydney University, Blacktown, NSW 2148, Australia.
² Storr Liver Centre, Westmead Institute for Medical Research, University of Sydney, Westmead, NSW, 2145, Australia.
³ Blacktown Hospital, Blacktown, NSW 2148, Australia.
⁴ Centre for Immunology and Allergy Research, Westmead Institute for Medical Research, Westmead, NSW 2145, Australia.
⁵ Westmead Clinical School, University of Sydney, Westmead, NSW 2145, Australia.
⁶ Westmead Hospital, Westmead, NSW 2145, Australia.

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.

Keywords: chronic infection; direct-acting antiviral; hepatitis C virus; interferon; natural killer cell.

Publication types

Review