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. RNA viruses, such as Zika and Dengue, activate the aryl hydrocarbon receptor (AHR) signaling to restrict the antiviral response. Here, the authors report that coronaviruses also activate AHR signaling, potentially allowing them to escape the immune response, and show that AHR antagonism limits SARS-CoV-2 replication in vitro, suggesting that AHR could be targeted for antiviral therapy.
【저자키워드】 Medical research, Infectious diseases, 【초록키워드】 SARS-CoV-2, pathology, antiviral therapy, Coronaviruses, immune response, Respiratory failure, COVID-19 pandemic, severity, Human, Infection, in vitro, Replication, Dengue, Viral load, viral replication, RNA viruses, single-cell RNA-seq, Mild, HCoV-229E, Zika, targets, AhR, respiratory tract, common cold, in vivo, antiviral immunity, expression, SARS-CoV-2 replication, Lung epithelial cells, COVID-19 patients, boost, Lung pathology, association, Signaling, antiviral response, Aryl hydrocarbon receptor, Analysis, epithelial cell, Activation, increased expression, SARS-CoV-2 infected patients, life-threatening, lung tissue, illnesses, viral titer, pharmacological, antagonist, Host, Future, limit, decrease, transcriptional, evaluate, activated, coronavirus, contribute, promote, restrict, suppressed, evade, activate, 【제목키워드】 Infection, AhR, Signaling, coronavirus,