title: Lysosomal localization and mechanism of membrane penetration influence nonenveloped virus activation of the NLRP3 inflammasome.
abstract: Adenovirus (Ad) endosomal membrane penetration activates the NLRP3 inflammasome by releasing lysosomal cathepsin B (catB) into the cytoplasm. We therefore examined the extent to which inflammasome activation correlates with Ad colocalization with catB-enriched lysosomes. Inflammasome activation, is greater during infections with Ad5 possessing an Ad16 fiber (Ad5F16gfp), or Ad5gfp neutralized by human serum, than Ad5gfp alone. Enhanced IL-1β release by Ad5F16gfp is partially due to increased TLR9 signaling but also correlates with greater release of catB into the cytoplasm. This increased TLR9 signaling and catB release correlates with a greater localization of Ad5F16gfp to lysosomes prior to endosomal escape. Another nonenveloped virus, reovirus, requires catB to penetrate cell membranes. However, reovirus did not release catB into the cytoplasm despite significantly greater colocalization with lysosomes compared to Ad5gfp and efficient membrane penetration. Thus, not only lysosomal localization, but the mechanism of membrane penetration influences viral activation of the NLRP3 inflammasome.
authors.affiliation: Department of Microbiology and Immunology, Loyola University Chicago, Stritch School of Medicine, Maywood, IL 60153, USA.
authors.forename: A U
authors.initials: AU
authors.lastname: Barlan
authors.forename: P
authors.initials: P
authors.lastname: Danthi
authors.forename: C M
authors.initials: CM
authors.lastname: Wiethoff
mesh_terms: D000256:Adenoviridae / Q000502:physiology*; D002352:Carrier Proteins / Q000378:metabolism*; D002401:Cathepsin B / Q000378:metabolism; D002460:Cell Line; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism*; D008247:Lysosomes / Q000821:virology*; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D012087:Reoviridae / Q000502:physiology; D051217:Toll-Like Receptor 9 / Q000378:metabolism; D014775:Virus Activation; D053586:Virus Internalization
chemical_list: D002352:Carrier Proteins; D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9; C533912:CTSB protein, human; D002401:Cathepsin B