Abstract
IntroductionPolymorphisms 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.MethodsWe 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.ResultsEarly 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.ConclusionsThese 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.
Highlights
Polymorphisms in the type III interferon IFN-l3 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
Acute infection outcome is determined by the interplay between the virus, the virus-specific immune response, and the host genetics such as polymorphisms in the IL28B/IFN-l3 locus, the killer cell immunoglobulin-like receptor (KIR) and HLA-C genes controlling the function of natural killer (NK) cells
These results suggest that early acute HCV is associated with variable type III IFNs plasma levels and that the favorable CC genotype is associated with higher viral load
Summary
Polymorphisms in the type III interferon IFN-l3 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. IFN-l3 single nucleotide polymorphism (SNP) (rs12979860) was associated with spontaneous HCV clearance [3, 4] with the favorable genotype designated as CC and the non-favorable as TT This SNP is located upstream of the IL28B (IFN-l3), IL28A (IFN-l2), and IL29 (IFN-l1) genes and it was postulated that it may control the transcription or the expression levels of type III IFNs but no clear association was established (reviewed in [5]). IFN-l3 rs12979860 SNP is in linkage disequilibrium of the coding sequence of another SNP upstream of IL28B controlling the expression of a relatively new member of the type III IFN family, IFN-l4, where reduced IFN-l4 activity was associated with improved HCV clearance and reduced expression of ISGs [9,10,11]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
