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Published online before print June 24, 2004
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,1
,
* Departments of Microbiology & Immunology and
Pediatrics and
Center of Research, Ste. Justine Hospital, University of Montreal, Quebec, Canada
1Correspondence: Laboratory of Immunovirology, Center of Research, Ste. Justine Hospital, 3175 Côte Ste-Catherine, Montreal, Qc, H3T 1C5, Canada. E-mail: ahmada{at}justine.umontreal.ca
Natural killer (NK) cells constitute the first line of host defense against invading pathogens. They usually become activated in an early phase of a viral infection. Liver is particularly enriched in NK cells, which are activated by hepatotropic viruses such as hepatitis C virus (HCV). The activated NK cells play an essential role in recruiting virus-specific T cells and in inducing antiviral immunity in liver. They also eliminate virus-infected hepatocytes directly by cytolytic mechanisms and indirectly by secreting cytokines, which induce an antiviral state in host cells. Therefore, optimally activated NK cells are important in limiting viral replication in this organ. This notion is supported by the observations that interferon treatment is effective in HCV-infected persons in whom it increases NK cell activity. Not surprisingly, HCV has evolved multiple strategies to counter host’s NK cell response. Compromised NK cell functions have been reported in chronic HCV-infected individuals. It is ironic that activated NK cells may also contribute toward liver injury. Further studies are needed to understand the role of these cells in host defense and in liver pathology in HCV infections. Recent advances in understanding NK cell biology have opened new avenues for boosting innate and adaptive antiviral immune responses in HCV-infected individuals.
Key Words: hepatitis C virus • natural killer cells • NK cell receptors • NK cell co-receptors
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