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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

Title: AHR signaling is induced by infection with coronaviruses.

Authors: Giovannoni, Federico; Li, Zhaorong; Remes-Lenicov, Federico; Dávola, María E; Elizalde, Mercedes; Paletta, Ana; Ashkar, Ali A; Mossman, Karen L; Dugour, Andrea V; Figueroa, Juan M; Barquero, Andrea A; Ceballos, Ana; Garcia, Cybele C; Quintana, Francisco J

Published In Nat Commun, (2021 Aug 26)

Abstract: Coronavirus infection in humans is usually associated to respiratory tract illnesses, ranging in severity from mild to life-threatening respiratory failure. The aryl hydrocarbon receptor (AHR) was recently identified as a host factor for Zika and dengue viruses; AHR antagonists boost antiviral immunity, decrease viral titers and ameliorate Zika-induced pathology in vivo. Here we report that AHR is activated by infection with different coronaviruses, potentially impacting antiviral immunity and lung epithelial cells. Indeed, the analysis of single-cell RNA-seq from lung tissue detected increased expression of AHR and AHR transcriptional targets, suggesting AHR signaling activation in SARS-CoV-2-infected epithelial cells from COVID-19 patients. Moreover, we detected an association between AHR expression and viral load in SARS-CoV-2 infected patients. Finally, we found that the pharmacological inhibition of AHR suppressed the replication in vitro of one of the causative agents of the common cold, HCoV-229E, and the causative agent of the COVID-19 pandemic, SARS-CoV-2. Taken together, these findings suggest that AHR activation is a common strategy used by coronaviruses to evade antiviral immunity and promote viral replication, which may also contribute to lung pathology. Future studies should further evaluate the potential of AHR as a target for host-directed antiviral therapy.

PubMed ID: 34446714 Exiting the NIEHS site

MeSH Terms: COVID-19/genetics; COVID-19/metabolism; COVID-19/virology; Coronavirus Infections/genetics; Coronavirus Infections/metabolism*; Coronavirus Infections/virology; Coronavirus/physiology*; Epithelial Cells/metabolism; Epithelial Cells/virology; Female; Humans; Male; Receptors, Aryl Hydrocarbon/genetics; Receptors, Aryl Hydrocarbon/metabolism*; SARS-CoV-2/physiology; Signal Transduction*

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