Type III Interferon (IFN) Induces a Type I IFN-Like Response in a Restricted Subset of Cells through Signaling Pathways Involving both the Jak-STAT Pathway and the Mitogen-Activated Protein Kinases

Abstract

IFN-functionally resembles type I IFN, inducing antiviral protection in vitro (10,23,27) as well as in vivo (1). Activation of the IFN-receptor leads to the phosphorylation of STAT1, STAT2, and STAT3 and the formation of the interferon-stimulated gene factor 3 (ISGF3) transcription factor (10) and to the induction of typical IFN-induced genes like the OAS and MxA genes. IFN-can reduce cell growth in vitro and possesses antitumor activity in several rodent models (11,25). However, a number of cytokines with very different biological effects activate STAT transcription factors, and pronounced functional differences between type I and type III IFNs exist. The in vivo antiviral activity of IFN-against herpes simplex virus 2 (HSV-2) has been shown to be comparable to that of IFN-␣ in a systemic model. However, a model for the clinically relevant vaginal HSV-2 infection revealed an antiviral activity of IFN-that surpassed that of IFN-␣ (1).The biological effect of the cytokine-receptor system is determined primarily by three factors: the expression profile of the cytokine itself, the expression profile of the receptor, and the set of target genes for regulation. We decided to start our investigation of the function of the IFN-system by asking which genes are regulated by IFN-. A gene array experiment covering the whole human genome revealed that all IFN--induced genes were also induced by type I IFN. Thus, no genes

Fish viperin exerts a conserved antiviral function through RLR-triggered IFN signaling pathway

“…involved in IFN response, which accords with the findings that this gene is highly upregulated by type I, II and III IFNs (Boudinot et al, 1999;Chin and Cresswell, 2001;Grewal et al, 2000;Zhou et al, 2007;Zhu et al, 1997), and by pivotal molecules of TLR and RLR signaling cascades (Severa et al, 2006). In addition, the activation of viperin mRNA accumulation by HCMV does not require the action of IFN and expression of viral genes (Zhu et al, 1997), indicating that there is IFN-independent pathways for induction of viperin.…”

Fish virus-induced interferon exerts antiviral function through Stat1 pathway

“…In general, type I and type III IFNs are directly induced by virus infection but not the type II IFN; therefore, type I together with type III constitutes a distinct subgroup known as "virus-induced IFNs". Although the two virus-induced IFN groups signal through a different receptor complex, both exhibit antiviral property through a similar mechanism that is characteristic of activation of the IFNstimulated gene factor 3 (ISGF-3) and induction of a similar set of downstream genes (Zhou et al, 2007).…”

Structure and function of interleukin-22 and other members of the interleukin-10 family

“…3). In the case of signaling by IFN-ks, a complex consisting of STAT1, STAT2, and p48 (IRF9), termed ISGF3, binds to interferon-stimulated response element (ISRE) promoting interferon-specific gene transcription [145,146]. All other members of the IL-10 family activate mainly STAT3.…”

“…The extracellular domain of class II cytokine receptors is responsible for its ligand binding and specificity. There is a partial overlap of CRF2s combination in IL-10 family signaling, but specificity is still attained by a specific receptor and/or interleukin expression by different cell types [145,146].…”