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: Mary K McCarthy, Danielle H Malitz, Caitlyn T Molloy, Megan C Procario, Kaitlyn E Greiner, Luna Zhang, Ping Wang, Sharlene M Day, Saul R Powell, Jason B Weinberg
• Journal: Virology (Virology) Vol. 498 Pg. 57-68 (11 2016) ISSN: 1096-0341 [Electronic] United States
• PMID: 27560373 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 Elsevier Inc. All rights reserved.

Chemical References

• Integrin beta Chains
• integrin beta5
• Interferon-gamma
• Interferons
• LMP7 protein
• Proteasome Endopeptidase Complex

Topics

• Adenoviridae (physiology)
• Adenoviridae Infections (immunology, metabolism, mortality, virology)
• Animals
• Immunomodulation (genetics, immunology)
• Integrin beta Chains (genetics, metabolism)
• Interferon-gamma (genetics, metabolism)
• Interferons (genetics, metabolism)
• Mice
• Mice, Knockout
• Myocarditis (genetics, immunology, metabolism, virology)
• Proteasome Endopeptidase Complex (genetics, metabolism)