Type III Interferons in Viral Infection and Antiviral Immunity

Abstract

Interferons (IFNs) can serve as the first line of immune defense against viral infection. The identification of IFN-λs 1, 2, 3 & 4 (termed as type III IFNs) has revealed that the antiviral immune response to viruses contains more components than the type I IFNs that have been known for more than 50 years. IFN-λs are IFN-λ1 (IL-29), IFN-λ2 (IL-28a), IFN-λ3 (IL-28b) and IFN-λ4, which resembles IFN-λ3. IFN-λs have type I-IFN-like immune responses and biological activities, but our knowledge of these novel players in the antiviral response is not well established. In this review, we try to describe the current information on the expression and function of IFN-λs in the innate antiviral immune defense and IFN-λ2’s role in regulating and shaping the adaptive immune response. We suggest that IFN-λs are key antiviral cytokines, directly performing an antiviral immune response at epithelial surfaces in the early stages of viral infection, and that these cytokines also skew the balance of Th1 and Th2 cells to Th1 phenotype. In addition, genetic polymorphisms in IFN-λ genes can impair antiviral immune responses in clinical treatment.

LYAR Suppresses Beta Interferon Induction by Targeting Phosphorylated Interferon Regulatory Factor 3

“…Further studies show that LYAR expression is increased in IFN-␤treated cells but is not induced by Sev in the IFN-I deficiency Vero cells, suggesting that LYAR is induced by IFN-␤ during viral infection. Interestingly, even if IFN-␣ and IFN-1 share similar properties with IFN-␤, especially IFN-␣, which is very similar to IFN-␤ in signaling pathways (34), they failed to stimulate LYAR expression in A549 cells, but it is unknown if it is also the case in other types of cells and whether higher concentrations and different time periods of treatment would make a difference. Although many genes induced by type I and III IFNs are shared, the kinetics of induction are distinct, and certain genes may be uniquely regulated by one of the subtypes (35,36), and it is therefore reasonable that LYAR expression is only induced by IFN-␤.…”

Innate Immune Evasion by Human Respiratory RNA Viruses

“…Recently, it has become clear that particular type III IFNs (IL-28/29), or IFN lambdas, which were discovered in 2003 [22,23], play a prominent role in defense of epithelial surfaces such as that in the lung (reviewed in [3,5,24]). They bind to a distinct heterodimeric receptor consisting of IFNLR1 and IL10RB (as opposed to type I IFN that binds to IFNAR1/2), but seem to trigger downstream signaling that is very similar to the type I IFN-induced pathways, and are also induced by the same PRRs as those triggering type I IFNs.…”

“…To facilitate comparison between the respiratory viruses described here, known and arguably important innate immune evasion strategies are listed, and for each strategy it is discussed how each virus group exploits its own mechanism. Innate immune evasion obviously links to the innate immune responses that are known to be elicited by respiratory and other (RNA) viruses, and while this will be elaborated to a limited extent below, they have also been reviewed comprehensively in recent reviews by others [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17].…”

Inhibition of PI3Kδ Enhances Poly I:C-Induced Antiviral Responses and Inhibits Replication of Human Metapneumovirus in Murine Lungs and Human Bronchial Epithelial Cells

“…Types I and III IFNs play important roles in immune responses to viral infection (12,40). Thus, we examined the effects of IC87114 on type I and type III IFNs responses in mouse lungs using real-time quantitative PCR.…”