Innate Immune Sensing of Influenza A Virus

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.

Differences on Pyrexia Related Immune Responses between SARS-CoV-2 and Influenza-A-infected Children: A Retrospective Study

“…SARS-CoV-2 infection was identi ed to activate the host innate immune system via the bindings of its spike glycoprotein (S-protein) to the angiotensin-converting enzyme 2 (ACE2) receptor and transmembrane protease serine 2 (TMPRSS2) [32,33], which engaged macrophages and monocytes to release cytokines and enhanced adaptive T and B cell immune response [34]. While in uenza infection is initiated by adhesion of hemagglutinin (HA) to sialic acids on the epithelial cells, followed with activation of innate immune signaling and further production of cytokines via host pathogen recognition receptors (PRPs) [35,36]. Further gene expression analyses have identi ed the expression pattern of cytokines, cytokine receptors, as well as transcription factors in COVID-19 patients, which quite differs from that of in uenza A infected patients [37,38].…”

Mammalian and Avian Host Cell Influenza A Restriction Factors

“…Viral PAMPs usually correspond to specific nucleic acid structures of the viral genome not found in host cells or viral replication intermediates such as double-stranded RNA (dsRNA). Distinct classes of PRRs are important for influenza virus recognition and induced inflammation ( Figure 2 ): the Toll-Like receptors (TLR), the Retinoic acid-inducible gene I (RIG-I) receptor, the NOD-like receptor family member NOD-, LRR- and pyrin-containing 3 (NLRP3) inflammasome and the Z-DNA binding protein 1 (ZBP1) (recently reviewed in [ 42 ]). These PRRs share different subcellular localizations and act at different stages of the viral replication cycle.…”

“…These PRRs share different subcellular localizations and act at different stages of the viral replication cycle. Indeed, NLRP3, RIG-I and ZBP1 are located in the cytoplasm, whereas TLR3, 7 and 8 are present within endosomes [ 42 ].…”

“…IAV has evolved various proteins such as NS1, PB1-F2 or PA-X to counteract the induction of innate immune responses either by inhibiting innate immune sensing or by inhibiting signaling downstream of type I or III IFN receptors (reviewed in [ 42 , 80 ]).…”

Special Issue: “Innate Immune Sensing of Viruses and Viral Evasion”

“…These publications exemplify the fact that viruses have evolved multiple ways to dampen the host IFN response by interfering, disrupting, or evading specific host regulators, both up-and downstream of IFN induction. The diverse viral escape pathways are described in the following reviews [7,8,[10][11][12][13] and one original article on herpes-viruses [14]. A recent discovery stems from the observation that DNA sensing by the cGAS/STING pathway can be triggered by certain RNA viruses.…”