Yonsei Med J.  2011 Nov;52(6):871-878. 10.3349/ymj.2011.52.6.871.

Clinical Implications of Chemokines in Acute and Chronic Hepatitis C Virus Infection

• Kang W
• Shin EC

• KMID: 1058805
• DOI: http://doi.org/10.3349/ymj.2011.52.6.871

Abstract

Hepatitis C virus (HCV), a non-cytopathic positive-stranded RNA virus, is one of the most common causes of chronic liver diseases such as chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Upon HCV infection, the majority of patients fail to clear the virus and progress to chronic hepatitis C. Chemokines are small chemotactic cytokines that direct the recruitment of immune cells and coordinate immune responses upon viral infection. Chemokine production during acute HCV infection contributes to the recruitment of immune cells with antiviral effector functions and subsequent viral clearance. In chronic HCV infection, however, continuous production of chemokines due to persistent viral replication might result in incessant recruitment of inflammatory cells to the liver, giving rise to persistence of chronic inflammation and liver injury. In this review, we will summarize the roles of chemokines in acute and chronic settings of HCV infection and the clinical relevance of chemokines in the treatment of hepatitis C.

Keyword

Hepatitis C virus; chemokine; inflammation; hepatitis

MeSH Terms

Antiviral Agents/therapeutic use
Chemokines/*metabolism
Hepatitis C/drug therapy/*immunology/*metabolism
Hepatitis C, Chronic/drug therapy/*immunology/*metabolism
Humans

Figure

• 

  Fig. 1 Schematic overview of Th1-associated chemokines and their receptors. Representative Th1-associated chemokine receptors are CXCR3 and CCR5. (A) CXCR3 is a receptor for CXCL9, CXCL10 and CXCL11, and is known to be expressed in Th1 CD4+ T cells and CD8+ T cells, especially in effector and effector memory subsets. (B) CCR5 is a receptor for CCL3, CCL4 and CCL5, though CCL3 and CCL5 bind to other receptors redundantly. CCR5 is also expressed in effector and effector memory subsets of Th1 CD4+ T cells and CD8+ T cells. MIG, monokine induced by interferon-γ; IP-10, interferon-γ-inducible protein-10; I-TAC, interferon-inducible T-cell α chemoattractant; MIP-1α, macrophage inflammatory protein-1α; MIP-1β, macrophage inflammatory protein-1β; RANTES, regulated on activation normal T cell expressed and secreted; Th1, T helper 1.

• 

  Fig. 2 Roles of chemokines in acute and chronic HCV infection. (A) During acute HCV infection, CXCR3- and CCR5-associated chemokines are produced at 2-8 weeks after HCV infection. The released chemokines contribute to viral clearance by recruiting effector Th1 CD4+ and CD8+ T cells. (B) In the majority of cases, however, viral clearance fails to accomplish, and HCV replication persists within the liver. The constant increase in the production of chemokines due to persistent HCV RNA replication results in continuous recruitment of inflammatory cells, both virus-specific and non-specific, to the liver and subsequent chronic liver injury without clearing the virus. HCV, hepatitis C virus.

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