Elsevier

Virus Research

Volume 323, 2 January 2023, 198962
Virus Research

Review
SARS-CoV-2 mediated dysregulation in cell signaling events drives the severity of COVID-19

https://doi.org/10.1016/j.virusres.2022.198962Get rights and content
Under a Creative Commons license
open access

Highlights

  • The TLRs and proximal signaling components are activated by SARS-CoV-2 infection.

  • Uncontrolled activation of NF-κB, whereas, a limited and delayed IFN induction may support increased viral replication with excessive pro-inflammatory cytokine secretion.

  • The activated NF-κB acts as a priming step for NLRP3 inflammasome formation and subsequent cell death in severe cases.

  • A number of underlying but dysregulated cellular components accelerate the pathogenesis.

Abstract

A balance in immune response against an unfamiliar pathogen is crucial to eliminate the infection. A cascade of cell signaling events is immediately activated upon sensing the presence of SARS-CoV-2 by cellular toll like receptors in a natural host response manner against the invading virus. The ultimate aim of such innate immune signaling pathways is to provide a required level of protection to our bodies by interfering with the invader. However, if there is any loss in such balance, an impairment in immune system emerge that fails to control the regulated transcription and translation of signaling components. Consequently, excessive level of proinflammatory mediators release into the circulatory systems that ultimately cause “cytokine storm” and COVID-19 pathological syndromes. The limited production of interferons (IFNs), while excessive yield of pro-inflammatory cytokines followed by SARS-CoV-2 infection suggests an abnormal cell signaling event and explains the reasons of increased immunopathology and severity in COVID-19.

Data availability

  • Data will be made available on request.

Cited by (0)

1

These authors contributed equally to this work.