Chemokine Regulation During Epidemic Coronavirus Infection

Abstract

SARS-CoV-2 (Severe Acute Respiratory Syndrome coronavirus-2) is the third coronavirus to emerge as a cause of severe and frequently fatal pneumonia epidemics in humans, joining SARS-CoV and MERS-CoV (Middle East Respiratory Syndrome-coronavirus). As with many infectious diseases, the immune response to coronavirus infection may act as a double-edged sword: necessary for promoting antiviral host defense, but, if not appropriately regulated, also able to incite life-threatening immunopathology. Key immunoregulatory mediators include the chemokines, a large family of leukocyte chemoattractants that coordinate leukocyte infiltration, positioning and activation in infected tissue by acting at specific G protein-coupled receptors. Here, we compare the involvement of chemokines and chemokine receptors during infection with the three epidemic coronaviruses and discuss their potential value as biomarkers and targets for therapeutic development.

Keywords: COVID-19; MERS; MERS-CoV; SARS; SARS-CoV; SARS-CoV-2.

Figure 1

Virulent CoVs cause ARDS by inducing a chemokine/cytokine storm in lungs. SARS-CoV, SARS-CoV-2 and MERS-CoV primarily infect type II pneumocytes in the alveoli. The first two viruses use ACE2 as their receptor, while MERS-CoV uses DPP4 to gain entry into cells. The viruses propagate and subsequently infect other cell types including alveolar macrophages to induce chemokines, which mediate the infiltration of inflammatory macrophages, neutrophils and T cells. Upon activation, these cells further the production of chemokines, that contribute towards pulmonary damage and the development of ARDS. Systemic chemokine/cytokine storm may result in multiple organ dysfunction syndrome and fatality. Application of chemokine receptor antagonists and anti-inflammatory molecules such as corticosteroids and BTK inhibitors may dampen the leukocyte infiltration in lungs, reducing the ensuing morbidity and mortality.