Divergent Roles of Autophagy in Virus Infection

Chiramel, Abhilash I.; Brady, Nathan R.; Bartenschlager, Ralf

The innate immune system is considered as the first line of defense against invading pathogens like viruses and bacteria. Upon viral infection, many cytosolic and endosomal immune sensors detect different components of viral nucleic acids to elicit an innate immune response. There are three classes of PRRs or immune sensors: Toll-like receptors (TLRs), retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) and nucleotide oligomerization domain (NOD)-like receptors (NLRs) [52] . TLRs are located either on the plasma membrane or within endosomal compartments. In contrast, RLRs and NLRs are mainly localized in the cytoplasm. Among the TLRs, TLR3, 7/8 and 9, which are mainly localized in endosomal compartments, recognize dsRNA, ssRNA and CpG DNA, respectively [52] . Many RNA viruses release their viral RNA genome into the cytoplasm to establish sites of RNA replication, thus allowing cytosolic PRRs to be activated [53] . However, activation of endosomal TLRs can be limited, because viral RNA is packed into the nucleocapsid or sequestered in membrane-associated replication complexes and thus, well protected from the endosomal environment. Nonetheless, TLRs frequently trigger an immune response targeting a number of viral infections via poorly defined mechanisms [54] .