AHR signaling is induced by infection with coronaviruses

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 immun...

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Detalhes bibliográficos
Autores: Giovannoni, Federico, Li, Zhaorong, Remes Lenicov, Federico, Dávola, María E., Elizalde, Maria Mercedes, Paletta, Ana Luz, Ashkar, Ali A., Mossman, Karen L., Dugour, Andrea Vanesa, Figueroa, Juan Manuel, Barquero, Andrea Alejandra, Ceballos, Ana, Garcia, Cybele, Quintana, Francisco Javier
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:Argentina
Recursos:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/182435
Acesso em linha:http://hdl.handle.net/11336/182435
Access Level:acceso abierto
Palavra-chave:ARYL HYDROCARBON RECEPTOR
COVID-19
SARS-COV-2
AHR ANTAGONIST
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
Descrição
Resumo: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.