Working Paper Review Version 1 This version is not peer-reviewed

Pathogenic Human Coronavirus Envelope Protein: A Clear Link to Immunopathology?

Version 1 : Received: 24 May 2020 / Approved: 25 May 2020 / Online: 25 May 2020 (17:54:57 CEST)

How to cite: Schoeman, D.; Fielding, B.C. Pathogenic Human Coronavirus Envelope Protein: A Clear Link to Immunopathology?. Preprints 2020, 2020050414 Schoeman, D.; Fielding, B.C. Pathogenic Human Coronavirus Envelope Protein: A Clear Link to Immunopathology?. Preprints 2020, 2020050414

Abstract

Since the severe acute respiratory syndrome (SARS) outbreak in 2003, human coronaviruses (hCoVs) have been identified as causative agents of severe acute respiratory tract infections. Two more hCoV outbreaks have since occurred, the most recent being SARS-CoV-2, the causative agent of coronavirus disease 2019 (COVID-19). The clinical presentation of SARS and MERS is remarkably similar to COVID-19, with hyperinflammation causing a severe form of the disease in some patients. Previous studies show that the expression of the SARS-CoV E protein is associated with the hyperinflammatory response that could culminate in acute respiratory distress syndrome (ARDS), a potentially fatal complication. This immune-mediated damage is largely caused by a cytokine storm, which is induced by significantly elevated levels of inflammatory cytokines interleukin (IL)-1beta and IL-6, which are partly mediated by the expression of the SARS-CoV E protein. The interaction between the SARS-CoV E protein and the host protein, syntenin, as well as the viroporin function of SARS-CoV E, are linked to this cytokine dysregulation. This review aims to compare the clinical presentation of virulent hCoVs with a specific focus on the cause of the immunopathology. The review also proposes that inhibition of IL-1beta and IL-6 in severe cases can improve patient outcome.

Subject Areas

human coronavirus; SARS-CoV; MERS-CoV; SARS-CoV-2; envelope protein; immunopathology

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