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AHR signaling is induced by infection with coronaviruses

Author

Listed:
  • Federico Giovannoni

    (Ann Romney Center for Neurologic Diseases, Brigham and Women’s Hospital, Harvard Medical School)

  • Zhaorong Li

    (Ann Romney Center for Neurologic Diseases, Brigham and Women’s Hospital, Harvard Medical School)

  • Federico Remes-Lenicov

    (Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Universidad de Buenos Aires)

  • María E. Dávola

    (Michael DeGroote Institute for Infectious Disease Research, McMaster University)

  • Mercedes Elizalde

    (Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Universidad de Buenos Aires)

  • Ana Paletta

    (Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Universidad de Buenos Aires)

  • Ali A. Ashkar

    (Michael DeGroote Institute for Infectious Disease Research, McMaster University)

  • Karen L. Mossman

    (Michael DeGroote Institute for Infectious Disease Research, McMaster University)

  • Andrea V. Dugour

    (Instituto de Ciencia y Tecnología Dr. Cesar Milstein (Consejo Nacional de Investigaciones Científicas y Técnicas-Fundacion Cassara))

  • Juan M. Figueroa

    (Instituto de Ciencia y Tecnología Dr. Cesar Milstein (Consejo Nacional de Investigaciones Científicas y Técnicas-Fundacion Cassara))

  • Andrea A. Barquero

    (Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires. CONICET- Instituto de Química Biológica (IQUIBICEN))

  • Ana Ceballos

    (Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Universidad de Buenos Aires)

  • Cybele C. Garcia

    (Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires. CONICET- Instituto de Química Biológica (IQUIBICEN))

  • Francisco J. Quintana

    (Ann Romney Center for Neurologic Diseases, Brigham and Women’s Hospital, Harvard Medical School
    Broad Institute of MIT and Harvard)

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.

Suggested Citation

  • Federico Giovannoni & Zhaorong Li & Federico Remes-Lenicov & María E. Dávola & Mercedes Elizalde & Ana Paletta & Ali A. Ashkar & Karen L. Mossman & Andrea V. Dugour & Juan M. Figueroa & Andrea A. Barq, 2021. "AHR signaling is induced by infection with coronaviruses," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25412-x
    DOI: 10.1038/s41467-021-25412-x
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    Cited by:

    1. Karolína Ondrová & Iveta Zůvalová & Barbora Vyhlídalová & Kristýna Krasulová & Eva Miková & Radim Vrzal & Petr Nádvorník & Binod Nepal & Sandhya Kortagere & Martina Kopečná & David Kopečný & Marek Šeb, 2023. "Monoterpenoid aryl hydrocarbon receptor allosteric antagonists protect against ultraviolet skin damage in female mice," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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