Chemokine Regulation During Epidemic Coronavirus Infection.

Shamik Majumdar,Philip M Murphy

doi:10.3389/fphar.2020.600369

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.

Highlights

The emergence and re-emergence of infectious agents in populations lacking pre-existing immunity is a bane of the human condition that has only worsened since the industrial revolution, primarily due to population growth, urban concentration, wild habitat encroachment and advances in transportation
When two Tg human ACE2 (hACE2) mouse strains with varying levels of hACE2 expression, AC70 and AC22, were compared, induction of Cxcl1, Ccl2 and Ccl5 in the lung was delayed in the strain susceptible to lethal SARS-CoV infection compared to the resistant Tg mice
Our focus on chemokine responses is motivated by the general importance of these molecules in coordinating immune responses and the tractability of G protein-coupled receptors (GPCRs) as targets for drug development

Summary

Introduction

The emergence and re-emergence of infectious agents in populations lacking pre-existing immunity is a bane of the human condition that has only worsened since the industrial revolution, primarily due to population growth, urban concentration, wild habitat encroachment and advances in transportation. Mice deficient in TMPRSS2 display reduced severity of disease following experimental SARS-CoV and MERS-CoV infection, including decreased lung pathology and dampened chemokine induction (Iwata-Yoshikawa et al, 2019a) (Tables 2 and 3).

Results

Conclusion