Interferon-Lambda: A Potent Regulator of Intestinal Viral Infections

Abstract

Interferon-lambda (IFN-λ) is a recently described cytokine found to be of critical importance in innate immune regulation of intestinal viruses. Endogenous IFN-λ has potent antiviral effects and has been shown to control multiple intestinal viruses and may represent a factor that contributes to human variability in response to infection. Importantly, recombinant IFN-λ has therapeutic potential against enteric viral infections, many of which lack other effective treatments. In this mini-review, we describe recent advances regarding IFN-λ-mediated regulation of enteric viruses with important clinical relevance including rotavirus, reovirus, and norovirus. We also briefly discuss IFN-λ interactions with other cytokines important in the intestine, and how IFN-λ may play a role in regulation of intestinal viruses by the commensal microbiome. Finally, we indicate currently outstanding questions regarding IFN-λ control of enteric infections that remain to be explored to enhance our understanding of this important immune molecule.

Astrovirus replication in human intestinal enteroids reveals multi-cellular tropism and an intricate host innate immune landscape

“…Type III IFN controls viral infections at the intestinal epithelial barrier [36] and the genes encoding IFN-λ were strongly upregulated in our RNA-seq dataset. Therefore, to evaluate the antiviral efficacy of type III IFN responses against VA1, J124, I124, D87 and I104 HIE were treated with IFN-λ (10 ng/ml) prior to infection and during infection (Fig 6E).…”

Host Factors Affecting Generation of Immunity Against Porcine Epidemic Diarrhea Virus in Pregnant and Lactating Swine and Passive Protection of Neonates

“…However, type I IFNs are more likely to induce antiviral effects systemically and are less effective at restricting viral replication in mucosal epithelial cells and clearing enteric viral pathogens like PEDV [49]. In contrast, recently identified type III IFNs (IFN-λ) are mainly produced by epithelial cells and are potent inducers of IFN-stimulated genes at the mucosal surface [50][51][52]. Many PEDV proteins have been identified that suppress IFN production, including nsp1, nsp3, nsp5, nsp7, nsp14, nsp15, nsp16, ORF3, E, M and N [53][54][55][56][57][58][59].…”

Epigenetic suppression of interferon lambda receptor expression leads to enhanced HuNoV replication in vitro

“…Subsequently, recruited signal transducer and activator of transcription 1 (STAT1) and STAT2 are activated through phosphorylation leading to the expression of IFN stimulated genes (ISGs), some of which have direct antiviral activities (Dickensheets et al ., 2013). Interferon lambdas are important players in both innate and adaptive immunity and have profound antiviral effects on a variety of viruses (Ank et al ., 2008; Mordstein et al ., 2010; Hemann et al ., 2017; Lee and Baldridge, 2017; Syedbasha and Egli, 2017). Expression of IFNLR1 on epithelial cells of the small intestine and colon was shown to be important in IFN-λ-mediated antiviral activity against persistent MNV and reovirus infection in vivo (Baldridge et al ., 2017).…”