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.
Highlights
Cells of the innate immune system utilize pattern recognition receptors (PRRs) to identify viral pathogens by engaging pathogen-associated molecular patterns (PAMPs)
This study indicates that the TLR3-mediated inflammatory response is beneficial in encephalomyocarditis virus (EMCV) infections; TLR3 signaling appears to be detrimental in a number of other viral infections
This study found that TLR3 driven production of inflammatory cytokines compromised the blood-brain barrier facilitating West Nile Virus (WNV) entry
Summary
Cells of the innate immune system utilize pattern recognition receptors (PRRs) to identify viral pathogens by engaging pathogen-associated molecular patterns (PAMPs). A diverse range of pathogens are sensed via recognition of their genomes or nucleic acids which accumulate during their replication Nowhere is this more prevalent than in viral detection. TLRs are type 1 transmembrane proteins that traffic between the plasma membrane and endosomal vesicles They are primarily responsible for detecting PAMPs in the extracellular environment. Those located on the plasma membrane are usually specific for hydrophobic lipids and proteins while those found in endosomes detect nucleic acids. This segregation appears intentional allowing innate cells to respond to components of the viral envelope such as fusion machinery at their surface. In addition to the production of proinflammatory molecules, many classes of PRRs mobilize the adaptive immune response by increasing expression of MHC class II and inducing expression of the costimulatory molecules CD40, CD80 and CD86
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