title: Interferon-dependent immunoproteasome activity during mouse adenovirus type 1 infection.
abstract: The immunoproteasome is an inducible host mechanism that aids in the clearance of damaged proteins. The immunoproteasome also influences immune function by enhancing peptide presentation by MHC class I and promotes inflammation via IκB degradation and activation of NF-κB. We used mouse adenovirus type 1 (MAV-1) to characterize the role of the immunoproteasome in adenovirus pathogenesis. Following intranasal infection of mice, immunoproteasome activity in the heart and lung was significantly increased in an IFN-γ-dependent manner. Absence of the β5i immunoproteasome subunit and pharmacological inhibition of β5i activity had minimal effects on viral replication, virus-induced cellular inflammation, or induction of cytokine expression. Likewise, the establishment of protective immunity following primary infection was not significantly altered by β5i deficiency. Thus, although immunoproteasome activity is robustly induced during acute infection with MAV-1, our data suggest that other mechanisms are capable of compensating for immunoproteasome activity to maintain antiviral immunity and appropriate inflammatory responses.
authors: Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI, USA.
authors: Mary K
authors: MK
authors: McCarthy
authors: Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, MI, USA.
authors: Danielle H
authors: DH
authors: Malitz
authors: Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, MI, USA.
authors: Caitlyn T
authors: CT
authors: Molloy
authors: Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, MI, USA.
authors: Megan C
authors: MC
authors: Procario
authors: Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, MI, USA.
authors: Kaitlyn E
authors: KE
authors: Greiner
authors: Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, MI, USA.
authors: Luna
authors: L
authors: Zhang
authors: Feinstein Institute for Medical Research, Manhasset, New York, USA.
authors: Ping
authors: P
authors: Wang
authors: Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
authors: Sharlene M
authors: SM
authors: Day
authors: Feinstein Institute for Medical Research, Manhasset, New York, USA.
authors: Saul R
authors: SR
authors: Powell
authors: Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI, USA; Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, MI, USA. Electronic address: jbwein@umich.edu.
authors: Jason B
authors: JB
authors: Weinberg
mesh_terms: D000256:Adenoviridae / Q000502:physiology*; D000257:Adenoviridae Infections / Q000276:immunology* / Q000378:metabolism* / Q000401:mortality / Q000821:virology; D000818:Animals; D056747:Immunomodulation / Q000235:genetics / Q000276:immunology; D039641:Integrin beta Chains / Q000235:genetics / Q000378:metabolism; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D007372:Interferons / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009205:Myocarditis / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000821:virology; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism*
chemical_list: D039641:Integrin beta Chains; C084344:integrin beta5; D007371:Interferon-gamma; D007372:Interferons; C077436:LMP7 protein; D046988:Proteasome Endopeptidase Complex
keywords: Adenovirus; Immunoproteasome; Inflammation; Interferon gamma; Myocarditis; Respiratory infection