Buffy Coat Transcriptomic Analysis Reveals Alterations in Host Cell Protein Synthesis and Cell Cycle in Severe

Liliane Tavares de Faria Cavalcante1, Guilherme Cordenonsi da Fonseca1, Luciane Almeida Amado Leon2

  • 1Laboratório de Bioinformática, Laboratório Nacional de Computação Científica, Petrópolis, Rio de Janeiro 25651-076, Brazil.

Insights

Severe COVID-19 disrupts host cell processes. Key pathways like translation and cell cycle are significantly altered, impacting disease severity. Fibrillarin is identified as a critical gene involved in these severe outcomes.

Area of Science:

  • Genomics
  • Molecular Biology
  • Virology

Background:

  • Transcriptome studies indicate cell cycle gene dysregulation and inhibited host mRNA translation in COVID-19.
  • Key genes and cellular mechanisms driving severe COVID-19 outcomes remain largely undefined.

Purpose of the Study:

  • To investigate differential gene expression in buffy coat cells from mild and severe COVID-19 patients.
  • To identify key genes and cellular pathways affected by severe acute respiratory syndrome (SARS)-CoV-2 infection.

Main Methods:

  • RNA-sequencing (RNA-seq) was employed to analyze gene expression profiles.
  • Differential gene expression and protein-protein interaction (interactome) analyses were performed.

Main Results:

  • 1009 genes were up-regulated and 501 down-regulated in severe COVID-19 patients.
  • Enriched pathways among down-regulated genes included ribosome and cell cycle.
  • Fibrillarin was identified as a key gene interacting with SARS-CoV-2 N protein and non-coding RNAs, affecting transcription and translation.

Conclusions:

  • Severe COVID-19 significantly alters host cell machinery, particularly translation and cell cycle processes.
  • Dysregulation of Fibrillarin is a critical factor in severe COVID-19 pathogenesis.
  • These findings highlight potential therapeutic targets for severe COVID-19.

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