IFN-λ3 polymorphism indirectly influences NK cell phenotype and function during acute HCV infection.

Introduction: Polymorphisms in the type III interferon IFN-λ3 and the killer cell immunoglobulin-like receptor (KIR) genes controlling the activity of natural killer (NK) cells can predict spontaneous resolution of acute hepatitis C virus (HCV) infection. We hypothesized that IFN-λ3 polymorphism may modulate NK cell function during acute HCV.

Methods: We monitored the plasma levels of type III IFNs in relation to the phenotype and the function of NK cells in a cohort of people who inject drugs (PWID) during acute HCV infection with different outcomes.

Results: Early acute HCV was associated with high variability in type III IFNs plasma levels and the favorable IFN-λ3 CC genotype was associated with higher viral loads. Reduced expression of Natural Killer Group Protein 2A (NKG2A) was associated with lower IFN-λ3 plasma levels and the CC genotype. IFN-γ production by NK cells was higher in individuals with the CC genotype during acute infection but this did not prevent viral persistence. IFN-λ3 plasma levels did not correlate with function of NK cells and IFN-λ3 prestimulation did not affect NK cell activation and function.

Conclusions: These results suggest that IFN-λ3 polymorphism indirectly influences NK cell phenotype and function during acute HCV but other factors may act in concert to determine the outcome of the infection.