Upregulation of Neuroinflammation-Associated Genes in the Brain of SARS-CoV-2-Infected Mice

Soo Jin Oh, Pratima Kumari, Tabassum Tasnim Auroni, Shannon Stone, Heather Pathak, Amany Elsharkawy, Janhavi Prasad Natekar, Ok Sarah Shin, Mukesh Kumar

Research output: Contribution to journalArticlepeer-review

Abstract

Neurological manifestations are a significant complication of coronavirus disease 2019 (COVID-19), but the underlying mechanisms are yet to be understood. Recently, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced neuroinvasion and encephalitis were observed in K18-hACE2 mice, leading to mortality. Our goal in this study was to gain insights into the molecular pathogenesis of neurological manifestations in this mouse model. To analyze differentially expressed genes (DEGs) in the brains of mice following SARS-CoV-2 infection, we performed NanoString gene expression analysis using three individual animal samples at 1, 3, and 6 days post-infection. We identified the DEGs by comparing them to animals that were not infected with the virus. We found that genes upregulated at day 6 post-infection were mainly associated with Toll-like receptor (TLR) signaling, RIG-I-like receptor (RLR) signaling, and cell death pathways. However, downregulated genes were associated with neurodegeneration and synaptic signaling pathways. In correlation with gene expression profiles, a multiplexed immunoassay showed the upregulation of multiple cytokines and chemokines involved in inflammation and cell death in SARS-CoV-2-infected brains. Furthermore, the pathway analysis of DEGs indicated a possible link between TLR2-mediated signaling pathways and neuroinflammation, as well as pyroptosis and necroptosis in the brain. In conclusion, our work demonstrates neuroinflammation-associated gene expression profiles, which can provide key insight into the severe disease observed in COVID-19 patients.

Original languageEnglish
Article number528
JournalPathogens
Volume13
Issue number7
DOIs
Publication statusPublished - 2024 Jul
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2024 by the authors.

Keywords

  • COVID-19
  • neuroinflammation
  • pyroptosis
  • SARS-CoV-2
  • TLR2 pathways

ASJC Scopus subject areas

  • Immunology and Allergy
  • Molecular Biology
  • General Immunology and Microbiology
  • Microbiology (medical)
  • Infectious Diseases

Fingerprint

Dive into the research topics of 'Upregulation of Neuroinflammation-Associated Genes in the Brain of SARS-CoV-2-Infected Mice'. Together they form a unique fingerprint.

Cite this