Organic Dust Exposure Enhances SARS-CoV-2 Entry in a PKC - and ADAM-17-Dependent Manner.

Details

• Alternative Title:
  International Journal of Translational Medicine (Basel, Switzerland), 2025, v. 4, no. 3: Organic Dust Exposure Enhances SARS-CoV-2 Entry in a PKC - and ADAM-17-Dependent Manner.
• Journal Article:
  International Journal of Translational Medicine (Basel, Switzerland)
• Personal Author:
  Muralidharan, Abenaya ; Bauer, Christopher D. ; Nissen, Claire G. ; Reid, St Patrick ; Poole, Jill A. ; Wyatt, Todd A.
• Description:
  SARS-CoV-2, the causative agent of the COVID-19 pandemic, has had a global impact, affecting millions over the last three years. Pre-existing lung diseases adversely affect the prognosis of infected COVID-19 patients, and agricultural workers routinely exposed to inhalable organic dusts have substantial increased risk for developing chronic lung diseases. In previous studies, we characterized the protein kinase C (PKC)-dependent airway inflammation mediated by organic dust extract (ODE) derived from dust collected from swine confinement facilities in in vitro and in vivo models. Here, we studied the effect of ODE on SARS-CoV-2 pseudoviral infection in mice and human bronchial epithelial cells (BEAS-2B). In wild-type (WT) and transgenic mice expressing the human angiotensin I-converting enzyme 2 (ACE2) receptor (SARS-CoV-2 entry receptor), ODE increased ACE2 shedding by ADAM-17 in the lungs. After repeated ODE treatments, the increased soluble ACE2 correlated to higher pseudovirus titer in the mouse lungs. In the human bronchial epithelial cells, ODE augmented PKCα activity in WT cells, and membrane ACE2 expression was diminished in PKCα-dominant negative cells. Unlike in the mice, increasing membrane ACE2 levels by treating with PKCα or ADAM-17 inhibitors and a low dose of ODE enhanced pseudoviral entry in vitro. Following viral entry, IL-8 secretion by the cells was diminished in a PKCα- and ADAM- 17-independent manner. Together, the complex mechanisms involved in the synergistic effects of agricultural dust and SARS-CoV-2 highlight the importance of studying dust-mediated changes to immunity against circulating pathogens.
• Content Notes:
  Author manuscript
• Subjects:
  • SARS-CoV-2
  • COVID-19
  • Farmers
  • Inflammation
  • Prognosis
  • Lung
  • Dust
• Keywords:
  • SARS-CoV-2
  • ACE2
  • organic dust (ODE)
  • PKCα
  • ADAM-17
• Source:
  International Journal of Translational Medicine (Basel, Switzerland), 2025, v. 4, no. 3
• DOI:
  https://doi.org/10.3390/ijtm4030032
• ISSN:
  2673-8937
• Pubmed ID:
  40160801
• Pubmed Central ID:
  PMC11951273
• Document Type:
  Text
• Funding:
  I01 BX005413/BX/BLRD VAUnited States/ ; IK6 BX003781/BX/BLRD VAUnited States/ ; IK6 BX005962/BX/BLRD VAUnited States/ ; U54 OH010162/OH/NIOSH CDC HHSUnited States/ ; R01 OH012045/OH/NIOSH CDC HHSUnited States/ ; I01 BX005886/BX/BLRD VAUnited States/
• Genre:
  Journal Article
• Pages in Document:
  486-497 (17 pdf pages)
• Volume:
  4
• Issue:
  3
• Download URL:
  https://stacks.cdc.gov/view/cdc/261546/cdc_261546_DS1.pdf
• File Type:
  [PDF - 1.15 MB]
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha-512:a4a409054fb4d0d929ae9c7525e28cf47bfba29f2c17fc87f08bb61c306ca135849804956b1267be414ca9d0455fbdceeef085a561f17cc5c91bd9b4a3ba8bda