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Updated: Jan 8, 2026

Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
08:32

Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production

Published on: March 2, 2014

10.9K

Spike protein-induced VSIR-ISX signaling disrupts metabolic homeostasis and promotes COVID-19-related immune

Li-Ting Wang1, Shen-Nien Wang2,3,4,5, Shyh-Shin Chiou6,7

  • 1Department of Life Science, National Taiwan Normal University, Taipei, Taiwan.

Cell Biology and Toxicology
|December 19, 2025
PubMed

Insights

The SARS-CoV-2 Spike protein disrupts metabolism via the VSIR-ISX pathway, impacting tryptophan and arachidonic acid pathways. Targeting this axis offers a potential therapeutic strategy for COVID-19.

Area of Science:

  • Molecular Biology
  • Immunology
  • Metabolic Research

Background:

  • COVID-19, caused by SARS-CoV-2, has led to significant global mortality.
  • Vaccine effectiveness is waning due to emerging viral variants, necessitating novel antiviral treatments.
  • Understanding virus-host interactions is crucial for developing effective therapies.

Purpose of the Study:

  • To investigate the mechanism by which the SARS-CoV-2 Spike protein (SARS-2-S) induces metabolic disturbances.
  • To identify the role of the VSIR-ISX signaling pathway in SARS-CoV-2-mediated metabolic alterations.
  • To explore the VSIR-ISX pathway as a potential therapeutic target for COVID-19.

Main Methods:

  • RNA sequencing to analyze gene expression changes in pulmonary cells.
  • Chromatin immunoprecipitation and genome sequencing to identify ISX binding sites.
  • Utilized shRNA interference and NF-κB inhibitors to disrupt the VSIR-ISX axis.

Main Results:

  • SARS-2-S expression activates genes in tryptophan and arachidonic acid (AA) metabolism, altering kynurenine and prostanoid levels.
  • The ACE2-MYD88 pathway, activated by SARS-2-S, enhances the VSIR-ISX axis via NF-κB signaling.
  • ISX directly binds to gene promoters, upregulating enzymes involved in AA metabolism.
  • Disruption of the VSIR-ISX axis mitigated SARS-2-S-induced metabolic disturbances.

Conclusions:

  • The VSIR-ISX signaling pathway is a key mediator of SARS-CoV-2-induced metabolic dysregulation.
  • Targeting the VSIR-ISX axis may offer a novel therapeutic strategy for managing COVID-19.
  • Intervention in metabolic pathways offers a new avenue for antiviral therapy development.
Keywords:
AA metabolic pathwayACE2COVID-19ISXNF-kappaB

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