Abstract
Influenza virus infection triggers host innate immune response by stimulating various pattern recognition receptors (PRRs). Activation of these PRRs leads to the activation of a plethora of signaling pathways, resulting in the production of interferon (IFN) and proinflammatory cytokines, followed by the expression of interferon-stimulated genes (ISGs), the recruitment of innate immune cells, or the activation of programmed cell death. All these antiviral approaches collectively restrict viral replication inside the host. However, influenza virus also engages in multiple mechanisms to subvert the innate immune responses. In this review, we discuss the role of PRRs such as Toll-like receptors (TLRs), Retinoic acid-inducible gene I (RIG-I), NOD-, LRR-, pyrin domain-containing protein 3 (NLRP3), and Z-DNA binding protein 1 (ZBP1) in sensing and restricting influenza viral infection. Further, we also discuss the mechanisms influenza virus utilizes, especially the role of viral non-structure proteins NS1, PB1-F2, and PA-X, to evade the host innate immune responses.
Highlights
The constant challenge to living cells by invading pathogens drives the evolution of innate immune systems to rapidly detect and respond to non-self molecules, such as virus-derived nucleic acids [1].Essential to the host’s innate immune responses to pathogens is to differentiate non-self molecules from self molecules, which is executed through pattern recognition receptors (PRRs) that recognize pathogen-associated molecular patterns (PAMPs), and in some cases, danger-associated molecular patterns (DAMPs) released by the infected host [2].Influenza A virus (IAV) infects a wide variety of species and is an important human respiratory pathogen that causes annual epidemics and occasionally pandemics, posing severe public health concerns
Ichinohe et al reported reduced expression of IL-1β, IL-18, and NLRP3 during influenza virus infection of antibiotic-treated mice suggesting a role of commensal bacteria in the priming of inflammasome [170]
Recent research has advanced our knowledge on how IAV infection is sensed by various PRRs and how the sensing triggers the signaling pathways, leading to the host innate immune responses
Summary
The constant challenge to living cells by invading pathogens drives the evolution of innate immune systems to rapidly detect and respond to non-self molecules, such as virus-derived nucleic acids [1]. L (RNase L) system is associated with NLRP3 activation as the release of IL-1β is minimal in IAV-infected RNase L-deficient BMDCs. The study reported that RNase L-cleaved RNA facilitates the formation of a complex containing RNA helicase DHX33, MAVS, and NLRP3 which results in NLRP3 activation in a DHX33 dependent manner [169]. Ichinohe et al reported reduced expression of IL-1β, IL-18, and NLRP3 during influenza virus infection of antibiotic-treated mice suggesting a role of commensal bacteria in the priming of inflammasome [170] Another NLR family member, NOD2 has been implicated in sensing the ssRNA genome of IAV and interacting with MAVS which leads to type I IFN induction via IRF3 [171]
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