Abstract
Type III interferons, also known as interferon lambdas (IFNλs), are the most recent addition to the IFN family following their discovery in 2003. Initially, IFNλ was demonstrated to induce expression of interferon-stimulated genes and exert antiviral properties in a similar manner to type I IFNs. However, while IFNλ has been described to have largely overlapping expression and function with type I IFNs, it has become increasingly clear that type III IFNs also have distinct functions from type I IFNs. In contrast to type I IFNs, whose receptor is ubiquitously expressed, type III IFNs signal and function largely at barrier epithelial surfaces, such as the respiratory and gastrointestinal tracts, as well as the blood–brain barrier. In further support of unique functions for type III IFNs, single nucleotide polymorphisms in IFNL genes in humans are strongly associated with outcomes to viral infection. These biological linkages have also been more directly supported by studies in mice highlighting roles of IFNλ in promoting antiviral immune responses. In this review, we discuss the current understanding of type III IFNs, and how their functions are similar to, and different from, type I IFN in various immune cell subtypes and viral infections.
Highlights
IFN lambda family members were initially named as interleukin-28 (IL-28) and IL-29 and classified into the IL-10 family genes as they signal through the common IL-10 receptor subunit 2 (IL-10R2) [7, 8]
Type III IFNs are produced more abundantly at mucosal sites by epithelial and myeloid cells in response to viral infection [31]. The mechanism for this preferential induction of type III IFN by intestinal epithelial cells (IECs) remains to be fully elucidated, but it might be due in part to the preferential induction of IFNλ upon mitochondrial antiviral signaling protein (MAVS) localization to peroxisomes, which are highly abundant in epithelial cells, following pathogen-associated molecular patterns (PAMPs) sensing [21]
Interferon lambda is important in a wide variety of viral infections that including hepatitis C virus (HCV), hepatitis B virus (HBV), influenza virus, rhinovirus, respiratory syncytial virus (RSV), lymphocytic choriomeningitis virus (LCMV), rotavirus, reovirus, norovirus, and West Nile virus (WNV) [reviewed in Ref. [17, 19, 44,45,46,47]]
Summary
Received: 04 October 2017 Accepted: 20 November 2017 Published: 06 December 2017. Citation: Hemann EA, Gale M Jr. and Savan R (2017) Interferon Lambda Genetics and Biology in Regulation of Viral Control. Type III interferons, known as interferon lambdas (IFNλs), are the most recent addition to the IFN family following their discovery in 2003. In further support of unique functions for type III IFNs, single nucleotide polymorphisms in IFNL genes in humans are strongly associated with outcomes to viral infection. These biological linkages have been more directly supported by studies in mice highlighting roles of IFNλ in promoting antiviral immune responses. We discuss the current understanding of type III IFNs, and how their functions are similar to, and different from, type I IFN in various immune cell subtypes and viral infections
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