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Neurobiological Alterations Induced by SARS-CoV-2: Insights from Variant-Specific Host Gene Expression Patterns in hACE2-Expressing Mice

  • 0Department of Biology, College of Arts and Sciences, Georgia State University, Atlanta, GA 30303, USA.
Viruses +

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March 27, 2025

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March 27, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

This study reveals how different SARS-CoV-2 variants impact the mouse brain transcriptome, showing shared immune responses and dysregulated genes like IL-6 across variants. These findings enhance our understanding of COVID-19 neurological effects.

Area Of Science

  • Neuroscience
  • Virology
  • Genomics

Background

  • Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants can cause neurological symptoms.
  • The specific impact of different SARS-CoV-2 variants on brain tissue remains largely unknown.

Purpose Of The Study

  • To conduct a comprehensive transcriptome analysis of mouse brain tissue infected with various SARS-CoV-2 variants.
  • To compare the molecular effects of ancestral and major SARS-CoV-2 variants of concern on the brain.

Main Methods

  • Whole-transcriptome analysis of K18-hACE2 mouse brains infected with SARS-CoV-2 variants (B.1, Alpha, Beta, Delta, Omicron).
  • Differential gene expression, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses.
  • Immune cell abundance profiling (ImmuCellAI) and RT-qPCR validation.

Main Results

  • Hierarchical clustering revealed distinct gene expression patterns between infected and control groups.
  • Pathway enrichment analyses showed similar patterns across different SARS-CoV-2 variants.
  • Significant alterations in immune cell populations, including decreased CD4+ T and B cells, and increased CD8+ T and dendritic cells.
  • Key genes such as STAT1, IL-6, and TNF-α were dysregulated in all variant infections.

Conclusions

  • This study provides the first extensive transcriptome analysis of mouse brains infected with major SARS-CoV-2 variants.
  • Shared molecular pathways and immune cell responses were observed across different variants.
  • Findings highlight conserved neuroinflammatory responses to SARS-CoV-2 variants.

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