Related Experiment Video

Updated: Nov 3, 2025

Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1β in Human Monocyte-derived Dendritic Cells
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Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1β in Human Monocyte-derived Dendritic Cells

Published on: May 22, 2014

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SARS-CoV-2 Nsp14 activates NF-κB signaling and induces IL-8 upregulation

Taiwei Li1, Adam D Kenney2, Helu Liu3

  • 1Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA.

Biorxiv : the Preprint Server for Biology
|June 2, 2021
PubMed

Insights

The SARS-CoV-2 Nsp14 protein activates NF-κB signaling, leading to inflammation. Inhibiting the host IMPDH2 protein blocks this activation and SARS-CoV-2 infection.

Area of Science:

  • Virology
  • Immunology
  • Molecular Biology

Background:

  • Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection triggers NF-κB activation and pro-inflammatory cytokine release, but the precise mechanisms remain unclear.
  • Understanding these pathways is crucial for developing effective antiviral strategies against COVID-19.

Approach:

  • Investigated the role of SARS-CoV-2 Nsp14 protein in NF-κB activation using cellular and molecular techniques.
  • Confirmed Nsp14-induced nuclear translocation of NF-κB p65 and upregulation of IL-6 and IL-8 cytokines.
  • Validated IL-8 upregulation in COVID-19 patient lung tissues.

Key Points:

  • Identified SARS-CoV-2 Nsp14 as a key contributor to NF-κB signaling activation.
  • Confirmed interaction between Nsp14 and host Inosine-5'-monophosphate dehydrogenase 2 (IMPDH2).
  • Demonstrated that IMPDH2 inhibition (using ribavirin or mycophenolic acid) abrogates Nsp14-mediated NF-κB activation and cytokine production.

Conclusions:

  • Nsp14-IMPDH2 interaction is essential for SARS-CoV-2-induced NF-κB activation and cytokine release.
  • IMPDH2 inhibitors effectively block SARS-CoV-2 replication, highlighting IMPDH2 as a potential therapeutic target.
  • This study reveals a novel mechanism by which SARS-CoV-2 manipulates host pathways to promote viral replication and inflammation.
Keywords:
IL-8IMPDH2NF-κBSARS-CoV-2mycophenolic acidribavirin

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