Open AccessThe IFN-λ4 Conundrum: When a Good Interferon Goes Bad
Author(s) -
Olusegun O. Onabajo,
Brian Muchmore,
Ludmila Prokunina–Olsson
Publication year - 2019
Publication title -
journal of interferon and cytokine research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.031
H-Index - 94
eISSN - 1557-7465
pISSN - 1079-9907
DOI - 10.1089/jir.2019.0044
Subject(s) - interferon , hepatitis c virus , allele , recombinant dna , biology , locus (genetics) , immunology , virology , virus , genetics , gene
Since its discovery in 2013, interferon lambda 4 (IFN-λ4) has received a reputation as a paradoxical type III IFN. Difficulties in detecting IFN-λ4, especially in secreted form even led to questions about its existence. However, the genetic ability to generate IFN-λ4, determined by the presence of the rs368234815-ΔG allele, is the strongest predictor of impaired clearance of hepatitis C virus (HCV) infection in humans. Significant modulation of IFN-λ4 activity by a genetic variant (P70S) supports IFN-λ4, and not other type III IFNs encoded in the same genomic locus, as the primary functional cause of the association with HCV clearance. Although the ability to produce IFN-λ4 is associated with decreased HCV clearance, the recombinant IFN-λ4 is active against HCV and other viruses. These observations present an apparent conundrum-when and how does a presumably good IFN, with anti-HCV activity, interfere with the ability to clear HCV? In this review, we discuss findings that suggest potential mechanisms for explaining this conundrum.