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

Area of Science:

• Environmental Health
• Virology
• Immunology

Background:

• COVID-19 pandemic caused by SARS-CoV-2 has global health implications.
• Pre-existing lung diseases worsen COVID-19 prognosis.
• Agricultural workers face increased risk of chronic lung diseases due to dust exposure.

Purpose of the Study:

• To investigate the effect of organic dust extract (ODE) on SARS-CoV-2 pseudoviral infection.
• To explore the role of protein kinase C (PKC) and ADAM-17 in ODE-mediated changes to ACE2 expression and viral entry.

Main Methods:

• Utilized in vitro (BEAS-2B human bronchial epithelial cells) and in vivo (mice) models.
• Administered ODE to wild-type and transgenic mice expressing human ACE2.
• Assessed ACE2 shedding, pseudovirus titers, PKCα activity, and IL-8 secretion.

Main Results:

• ODE increased ACE2 shedding by ADAM-17 in mouse lungs, correlating with higher pseudovirus titers.
• In human cells, ODE augmented PKCα activity, diminishing membrane ACE2 expression.
• In vitro, enhancing membrane ACE2 with inhibitors and low ODE dose increased viral entry, but IL-8 secretion was reduced independently of PKCα/ADAM-17.

Conclusions:

• ODE influences SARS-CoV-2 entry through complex mechanisms involving ACE2 regulation.
• Dust exposure can synergistically affect viral infection susceptibility and immune responses.
• Further research is crucial to understand dust-mediated immune alterations against pathogens.