Interferon lambda induces antiviral response to herpes simplex virus 1 infection

Abstract

Summary. -Lambda interferons (IFN-λ) are known to induce potent antiviral response in a wide variety of target cells. They activate the same intracellular signalling pathways and have similar biological activities as IFN-α/β, including antiviral activity, but signal via distinct receptor complex, which is expressed in a celland species-specific manner. IFN-λ was reported to induce in vitro marked antiviral activity against various RNA viruses, but corresponding data on DNA viruses are sparse. Therefore we examined the IFN-λ1 induced antiviral activity against two strains of herpes simplex virus 1, a highly pathogenic ANGpath and moderately pathogenic KOS. The antiviral response was determined in vitro in Vero cells, known as deficient in production of type I IFNs and in Vero E6 cells, responding to viral infection with abundant IFN-λ production, although deficient in production of type I IFNs. The results showed that IFN-λ1 induced in Vero cells higher antiviral activity against ANGpath strain than against KOS strain. In Vero E6 cells endogenous IFN-λ induced higher antiviral activity against ANGpath strain than against KOS strain, but because of the virus induction of IFN-λ expression the antiviral activity was detected later. The observed differences between the IFN-λ1-induced antiviral activities against viral strains of various pathogenicity suggest that virus attributes may play role in the antiviral state of cells induced by IFN-λ.

Herpes Simplex Virus 1 and 2 Vaccine Design: What can we Learn from the Past?

“…The type III IFNs, also designated as IFN-λ1, IFN-λ2 and IFN-λ3 (IL-29, IL-28A, and IL-28B), have been recently characterized; alike to classical type I IFNs, also IFN-λ induces production of antiviral substances in the infected cells [37]. The participation of type III IFNs in inhibition of HSV replication has been confirmed in vitro [38,39].…”

Differential roles of interferons in innate responses to mucosal viral infections

“…Type III IFNs were initially identified as key antiviral cytokines in the context of murine genital HSV-2 infection, with IFN-λ treatment blocking virus replication in the vaginal mucosa [29]. These findings have since been confirmed in vitro in simian Vero cells as well as primary human astrocytes and neurons, thus indicating that type III IFNs exhibit potent restriction of HSV replication in mucosal epithelial cells as well as in CNS cells [106,107]. Of interest, type III IFNs have been implicated in the maintenance of the blood-brain barrier during WNV and rabies virus infections in mice, with Ifnlr1 -/mice exhibiting enhanced spread to the brain and IFN-λ treatment in them helping to maintain tight junction and barrier integrity [108,109].…”

High-risk Allele for Herpes Labialis Severity at the IFNL3/4 Locus is Associated With Vestibular Neuritis

“…IFN- λs (or type III IFNs) mediate antiviral, antibacterial and antifungal effects, with the four previously known INF- λ ligands (IFN- λ1-4) having different affinities to their receptor (IFNLR), which is a heterodimer consisting of an a- (IL28RA) and a b-subunit (IL10RB) showing a highly variable cell type specific expression pattern [for review see ( 24 )]. Similar to type I IFNs (IFN-α and β), IFN- λs are able to inhibit replication of several virus types, e.g., HSV-1 ( 25 ), HSV-2 ( 26 ), and HCV ( 27 ). However, IFN- λ4 differs from the other type III IFNs in its kinetics, its earlier release during viral infections and its ability to induce the expression of genes that negatively regulate IFN response ( 28 ).…”