NEW YORK (Reuters Health) - Only about 20% of people exposed to hepatitis C virus (HCV) naturally clear the infection. New research suggests that the host response depends in part on the phenotype of natural killer (NK) cells, the lymphocytes that secrete cytokines and kill infected cells.
Senior investigator Dr. Mary Carrington and associates determined the genotype of 1037 individuals exposed to HCV, 352 of whom resolved the infection. Specifically, they examined the genotype of killer cell immunoglobulin-like receptors (KIR) on NK cells and the genotype of the corresponding human leukocyte antigen C group 1 (HLA-C1) ligand.
Ordinarily, KIR receptors suppress the action of the NK cells so they will not attack otherwise healthy cells, the researchers explain in the August 6th issue of Science. If the KIR-HLA interaction is weaker, the NK cell can become activated and thus rid the body of infected cells.
“We know that NK cells enter the liver of individuals infected with HCV, apparently to try to clear the viral infection,” Dr. Carrington, a researcher at the National Cancer Institute in Frederick, Maryland, told Reuters Health. “Because KIR receptors regulate the activity of NK cells, causing them to become inhibited or activated, we thought it made sense to look at these genes among those with persistent or cleared infection.”
The investigators did observe differences between groups. Individuals homozygous for HLA-C1 and KIR2DL3 resolved HCV infection more frequently than did those with other genotypes (odds ratio (OR) for clearance, 1.71, p = 0.003).
The relationship was even stronger among the subset of patients who were infected with a low inoculum of HCV, as would be found in needlestick injuries compared with those infected by blood transfusions (in multivariate analysis, OR = 2.24, p = 0.001).
“This combination of HLA and KIR transmits a weaker inhibitory signal to NK cells than other combinations, which translates into stronger activation of those cells,” Dr. Carrington explained. “This says that activation of NK cells in the liver is a good thing for clearance of HCV.”
Further research will be required before these findings can be applied clinically, she said. But eventually, “it’s possible that if we could activate NK cells in the liver after infection, maybe that could enhance clearance of the virus.”
For example, “perhaps soluble ligands could be applied in a localized manner in the liver to enhance NK cell activation, or antibodies that would bind to an activating receptor could be injected.”
Source: Science 2004;305:872-874. [ Google search on this article ]
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