Pattern Recognition Receptors and the Innate Immune Response to Viral Infection

Abstract

The innate immune response to viral pathogens is critical in order to mobilize protective immunity. Cells of the innate immune system detect viral infection largely through germline-encoded pattern recognition receptors (PRRs) present either on the cell surface or within distinct intracellular compartments. These include the Toll-like receptors (TLRs), the retinoic acid-inducble gene I-like receptors (RLRs), the nucleotide oligomerization domain-like receptors (NLRs, also called NACHT, LRR and PYD domain proteins) and cytosolic DNA sensors. While in certain cases viral proteins are the trigger of these receptors, the predominant viral activators are nucleic acids. The presence of viral sensing PRRs in multiple cellular compartments allows innate cells to recognize and quickly respond to a broad range of viruses, which replicate in different cellular compartments. Here, we review the role of PRRs and associated signaling pathways in detecting viral pathogens in order to evoke production of interferons and cytokines. By highlighting recent progress in these areas, we hope to convey a greater understanding of how viruses activate PRR signaling and how this interaction shapes the anti-viral immune response.

Toll-like receptors, signaling adapters and regulation of the pro-inflammatory response by PI3K

“…Activation of IRF transcription factors through TLR stimulation is accomplished through both the MyD88-dependent and TRIF-dependent signaling pathways upon ligand binding. 48 The MyD88-dependent pathway leads to IRF7 activation upon stimulation of TLR7, TLR8 or TLR9. 49 Ligand binding leads to an interaction of IRF7 with MyD88 through its death domain.…”

The New World arenavirus Tacaribe virus induces caspase-dependent apoptosis in infected cells

“…Apoptosis is the process of programmed cell death and plays an important role in the host response to virus infection (Thompson et al, 2011). Apoptosis can be initiated via the extrinsic pathway, mediated by death receptors of the TNF-family on the cell surface (Ashkenazi & Dixit, 1998), as well as the intrinsic pathway, triggered by the release of cytochrome c from the inner mitochondrial membrane into the cytosol (Granville & Gottlieb, 2002).…”

Poxviral Protein A46 Antagonizes Toll-like Receptor 4 Signaling by Targeting BB Loop Motifs in Toll-IL-1 Receptor Adaptor Proteins to Disrupt Receptor:Adaptor Interactions

“…The anti-viral roles of TLR3, -7, -8, and -9, which recognize viral nucleic acids and mount a potent antiviral response by inducing type I IFNs, are well established (4). TLR2, known to recognize bacterial ligands, is also involved in the recognition of viral glycoproteins, leading to the induction of proinflammatory responses (5), and TLR2 has recently been shown to be required in vivo in specific cell types for the induction of type I IFN in response to the poxvirus vaccinia virus (VACV) (6). TLR4, although best known for its role in recognizing LPS, also plays a role in the immune response to viruses.…”