Immunoproteasomes as a novel antiviral mechanism in rhinovirus-infected airways

Kris Genelyn Dimasuay, Amelia Sanchez, Niccolette Schaefer, Jorge Polanco, Deborah A Ferrington, Hong Wei Chu

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1711-1723
Number of pages13
JournalClinical science
Volume132
Issue number15
DOIs
StatePublished - Aug 1 2018

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Rhinovirus
Antiviral Agents
Epithelial Cells
Infection
Interferons
Viral Load
Messenger RNA
Histocompatibility Antigens Class I
Bronchoalveolar Lavage Fluid
Antigen Presentation
Virus Diseases
Chronic Obstructive Pulmonary Disease
Genes
Neutrophils
Anti-Inflammatory Agents
Up-Regulation
Asthma
Epithelium
Air

Cite this

Dimasuay, K. G., Sanchez, A., Schaefer, N., Polanco, J., Ferrington, D. A., & Chu, H. W. (2018). Immunoproteasomes as a novel antiviral mechanism in rhinovirus-infected airways. Clinical science, 132(15), 1711-1723. https://doi.org/10.1042/CS20180337

Immunoproteasomes as a novel antiviral mechanism in rhinovirus-infected airways. / Dimasuay, Kris Genelyn; Sanchez, Amelia; Schaefer, Niccolette; Polanco, Jorge; Ferrington, Deborah A; Chu, Hong Wei.

In: Clinical science, Vol. 132, No. 15, 01.08.2018, p. 1711-1723.

Research output: Contribution to journalArticle

Dimasuay, KG, Sanchez, A, Schaefer, N, Polanco, J, Ferrington, DA & Chu, HW 2018, 'Immunoproteasomes as a novel antiviral mechanism in rhinovirus-infected airways', Clinical science, vol. 132, no. 15, pp. 1711-1723. https://doi.org/10.1042/CS20180337
Dimasuay, Kris Genelyn ; Sanchez, Amelia ; Schaefer, Niccolette ; Polanco, Jorge ; Ferrington, Deborah A ; Chu, Hong Wei. / Immunoproteasomes as a novel antiviral mechanism in rhinovirus-infected airways. In: Clinical science. 2018 ; Vol. 132, No. 15. pp. 1711-1723.
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