IFN-λ3 polymorphism indirectly influences NK cell phenotype and function during acute HCV infection.
BACKGROUND
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.
Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM) Montréal Québec Canada.
Marion
M
Depla
Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM)MontréalQuébecCanada; Département de microbiologie et immunologieFaculté de médecineUniversité de MontréalMontréalQuébecCanada.
Sandy
S
Pelletier
Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM) Montréal Québec Canada.
Nathalie
N
Bédard
Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM)MontréalQuébecCanada; Département de microbiologie et immunologieFaculté de médecineUniversité de MontréalMontréalQuébecCanada.
Camille
C
Brunaud
Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM)MontréalQuébecCanada; Département de médecine familiale et de médecine d'urgenceFaculté de médecineUniversité de MontréalMontréalQuébecCanada.
Julie
J
Bruneau
Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM)MontréalQuébecCanada; Département de médecineFaculté de médecineUniversité de MontréalMontréalQuébecCanada.
Naglaa H
NH
Shoukry
Hepatitis C; NK cells; Type III IFN