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 activa...

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Bibliographic Details
Published in:Virology (New York, N.Y.) N.Y.), 2011-04, Vol.412 (2), p.306-314
Main Authors: Barlan, A.U, Danthi, P, Wiethoff, C.M
Format: Article
Language:English
Subjects:
Adenoviridae - physiology
Adenovirus
Carrier Proteins - metabolism
Cathepsin B
Cathepsin B - metabolism
Cell Line
Fiber
Humans
Infectious Disease
Inflammasome
Inflammasomes - metabolism
Lysosomes
Lysosomes - virology
NLR Family, Pyrin Domain-Containing 3 Protein
Nonenveloped virus
Reoviridae - physiology
Reovirus
Toll-Like Receptor 9 - metabolism
Virus Activation
Virus Internalization
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Summary: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.
ISSN:0042-6822
1096-0341
DOI:10.1016/j.virol.2011.01.019