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Immunomodulatory Function of Interleukin 28B During Primary Infection With Cytomegalovirus
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Immunomodulatory Function of Interleukin 28B During Primary Infection With Cytomegalovirus
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Journal Article
Immunomodulatory Function of Interleukin 28B During Primary Infection With Cytomegalovirus
2014
Overview
Background. Feedback mechanisms between interferons α and λ (IFNs) may be affected by single nucleotide polymorphisms (SNP) in interleukin 28B (IL-28B; IFN-λ3) promoter region and may influence cytomegalovirus (CMV) replication. Methods. We associated IL-28B SNPs with the risk of CMV replication after transplantation. Next, we examined the effect of IL-28B genotypes on IL-28B, and IFN-stimulated gene (ISG) expression, and CMV replication in human foreskin fibroblast (HFF) and peripheral blood mononuclear cells (PBMCs). Results. Transplant recipients with an IL-28B SNP (rs8099917) had significantly less CMV replication (P = .036). Both HFF-cells and PBMCs with a SNP showed lower IL-28B expression during infection with CMV, but higher \"antiviral\" ISG expression (eg, OAS1). Fibroblasts with a SNP had a 3-log reduction of CMV replication at day 4 (P = .004). IL-28B pretreatment induced ISG expression in noninfected fibroblasts, but a relative decrease of ISG expression could be observed in CMV-infected fibroblasts. The inhibitory effects of IL-28B could be abolished by siRNA or antagonistic peptides against the IL-28 receptor. In fibroblasts, inhibition of IL-28 signaling resulted in an increase of ISG expression and 3-log reduction of CMV-replication (P = .01). Conclusions. We postulate that IL-28B may act as a key regulator of ISG expression during primary CMV infection. IL-28B SNPs may be associated with higher antiviral ISG expression, which results in better replication control.
Publisher
Oxford University Press
Subject
/ Aged
/ Biological and medical sciences
/ Cytomegalovirus - immunology
/ Cytomegalovirus - physiology
/ Cytomegalovirus Infections - genetics
/ Cytomegalovirus Infections - immunology
/ Female
/ Fundamental and applied biological sciences. Psychology
/ Genetic Predisposition to Disease
/ Humans
/ Leukocytes, Mononuclear - virology
/ Male
/ Polymorphism, Single Nucleotide
/ VIRUSES
