title: Mouse Norovirus infection promotes autophagy induction to facilitate replication but prevents final autophagosome maturation.
abstract: Autophagy is a cellular process used to eliminate intracellular pathogens. Many viruses however are able to manipulate this cellular process for their own advantage. Here we demonstrate that Mouse Norovirus (MNV) infection induces autophagy but does not appear to utilise the autophagosomal membrane for establishment and formation of the viral replication complex. We have observed that MNV infection results in lipidation and recruitment of LC3 to the autophagosome membrane but prevents subsequent fusion of the autophagosomes with lysosomes, as SQSTM1 (an autophagy receptor) accumulates and Lysosome-Associated Membrane Protein1 is sequestered to the MNV replication complex (RC) rather than to autophagosomes. We have additionally observed that chemical modulation of autophagy differentially affects MNV replication. From this study we can conclude that MNV infection induces autophagy, however suppresses the final maturation step of this response, indicating that autophagy induction contributes to MNV replication independently of RC biogenesis.
authors.affiliation: Department of Microbiology and Immunology, at the Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne 3010, Australia.
authors.forename: Tanya B
authors.initials: TB
authors.lastname: O'Donnell
authors.affiliation: School of Chemical and Biological Sciences, University of Queensland, St. Lucia, Brisbane, Queensland 4072, Australia.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Hyde
authors.affiliation: Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Melbourne 3010, Australia.
authors.forename: Justine D
authors.initials: JD
authors.lastname: Mintern
authors.affiliation: Department of Microbiology and Immunology, at the Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne 3010, Australia. Electronic address: jason.mackenzie@unimelb.edu.au.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Mackenzie
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001343:Autophagy / Q000235:genetics*; D002460:Cell Line; D002522:Chlorocebus aethiops; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism / Q000648:ultrastructure / Q000821:virology; D051907:Lysosomal Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000821:virology*; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism; D029322:Norovirus / Q000235:genetics* / Q000378:metabolism; D010588:Phagosomes / Q000378:metabolism / Q000648:ultrastructure / Q000821:virology*; D000071456:Sequestosome-1 Protein; D015398:Signal Transduction; D014709:Vero Cells; D014779:Virus Replication / Q000235:genetics; D052118:Lysosomal-Associated Membrane Protein 1
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D006360:Heat-Shock Proteins; D051907:Lysosomal Membrane Proteins; D008869:Microtubule-Associated Proteins; D000071456:Sequestosome-1 Protein; C052255:Lamp1 protein, mouse; D052118:Lysosomal-Associated Membrane Protein 1; C480860:Map1lc3b protein, mouse; C101343:Sqstm1 protein, mouse
keywords: Autophagy; Mouse Norovirus; Virus replication