Rhinovirus (RV) infection is involved in acute exacerbations of asthma and chronic obstructive pulmonary disease (COPD). RV primarily infects upper and lower airway epithelium. Immunoproteasomes (IP) are proteolytic machineries with multiple functions including the regulation of MHC class I antigen processing during viral infection. However, the role of IP in RV infection has not been explored. We sought to investigate the expression and function of IP during airway RV infection. Primary human tracheobronchial epithelial (HTBE) cells were cultured at air–liquid interface (ALI) and treated with RV16, RV1B, or interferon (IFN)-λ in the absence or presence of an IP inhibitor (ONX-0914). IP gene (i.e. LMP2) deficient mouse tracheal epithelial cells (mTECs) were cultured for the mechanistic studies. LMP2-deficient mouse model was used to define the in vivo role of IP in RV infection. IP subunits LMP2 and LMP7, antiviral genes MX1 and OAS1 and viral load were measured. Both RV16 and RV1B significantly increased the expression of LMP2 and LMP7 mRNA and proteins, and IFN-λ mRNA in HTBE cells. ONX-0914 down-regulated MX1 and OAS1, and increased RV16 load in HTBE cells. LMP2-deficient mTECs showed a significant increase in RV1B load compared with the wild-type (WT) cells. LMP2-deficient (compared with WT) mice increased viral load and neutrophils in bronchoalveolar lavage (BAL) fluid after 24 h of RV1B infection. Mechanistically, IFN-λ induction by RV infection contributed to LMP2 and LMP7 up-regulation in HTBE cells. Our data suggest that IP are induced during airway RV infection, which in turn may serve as an antiviral and anti-inflammatory mechanism.
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August 2018
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A depiction of the mechanism of cellular autophagy showing the fusion of a lysosome with an autophagosome. The various molecules involved in the process can be seen alongside different microbes within the autophagosome. In this issue of Clinical Science, Li et al. (issue 15, pages 1645–1667) investigate the role of HMGB1-induced autophagy in liver fibrosis, and Andrade-Silva et al. (issue 16, pages 1725–1739) discuss the involvement of TLR2 and TLR4 in autophagy associated with cisplatin-induced acute kidney injury.
Research Article|
August 16 2018
Immunoproteasomes as a novel antiviral mechanism in rhinovirus-infected airways
Kris Genelyn Dimasuay;
Kris Genelyn Dimasuay
1Department of Medicine, National Jewish Health, Denver, CO, U.S.A.
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Amelia Sanchez;
Amelia Sanchez
1Department of Medicine, National Jewish Health, Denver, CO, U.S.A.
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Niccolette Schaefer;
Niccolette Schaefer
1Department of Medicine, National Jewish Health, Denver, CO, U.S.A.
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Jorge Polanco;
Jorge Polanco
2Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, MN, U.S.A.
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Deborah A. Ferrington;
2Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, MN, U.S.A.
Correspondence: Hong Wei Chu ([email protected]) or Deborah A. Ferrington ([email protected])
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Hong Wei Chu
1Department of Medicine, National Jewish Health, Denver, CO, U.S.A.
Correspondence: Hong Wei Chu ([email protected]) or Deborah A. Ferrington ([email protected])
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Publisher: Portland Press Ltd
Received:
April 18 2018
Revision Received:
June 29 2018
Accepted:
July 05 2018
Accepted Manuscript online:
July 06 2018
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2018
Clin Sci (Lond) (2018) 132 (15): 1711–1723.
Article history
Received:
April 18 2018
Revision Received:
June 29 2018
Accepted:
July 05 2018
Accepted Manuscript online:
July 06 2018
Citation
Kris Genelyn Dimasuay, Amelia Sanchez, Niccolette Schaefer, Jorge Polanco, Deborah A. Ferrington, Hong Wei Chu; Immunoproteasomes as a novel antiviral mechanism in rhinovirus-infected airways. Clin Sci (Lond) 16 August 2018; 132 (15): 1711–1723. doi: https://doi.org/10.1042/CS20180337
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