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Journal Article Epublish 10 citations

PubMed: 36362378 DOI: 10.3390/ijms232113588

Buffy Coat Transcriptomic Analysis Reveals Alterations in Host Cell Protein Synthesis and Cell Cycle in Severe COVID-19 Patients.

Int J Mol Sci 23(21)

Authors: Liliane Tavares de Faria Cavalcante, Guilherme Cordenonsi da Fonseca, Luciane Almeida Amado Leon, Andreza Lemos Salvio, Otávio José Brustolini, Alexandra Lehmkuhl Gerber, Ana Paula de Campos Guimarães, Carla Augusta Barreto Marques, Renan Amphilophio Fernandes, Carlos Henrique Ferreira Ramos Filho, Rafael Lopes Kader, Marisa Pimentel Amaro, João Paulo da Costa Gonçalves, Soniza Vieira Alves-Leon, Ana Tereza Ribeiro Vasconcelos

Affiliations

  • Laboratório de Bioinformática, Laboratório Nacional de Computação Científica, Petrópolis, Rio de Janeiro 25651-076, Brazil.
  • Laboratório de Desenvolvimento Tecnológico em Virologia, Instituto Oswaldo Cruz/FIOCRUZ, Rio de Janeiro 21040-360, Brazil.
  • Laboratório de Neurociências Translacional, Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro 20211-040, Brazil.
  • Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-617, Brazil.
  • Laboratory of Translacional Neurosciences, Biomedical Institute, Universidade Estadual do Rio de Janeiro, Rio de Janeiro 20550-013, Brazil.
  • Yale New Haven Hospital, New Haven, CT 06510, USA.
  • Laboratório de Neurociências Translacional, Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro 20211-040, Brazil. Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-617, Brazil.

Abstract

Transcriptome studies have reported the dysregulation of cell cycle-related genes and the global inhibition of host mRNA translation in COVID-19 cases. However, the key genes and cellular mechanisms that are most affected by the severe outcome of this disease remain unclear. For this work, the RNA-seq approach was used to study the differential expression in buffy coat cells of two groups of people infected with SARS-CoV-2: (a) Mild, with mild symptoms; and (b) SARS (Severe Acute Respiratory Syndrome), who were admitted to the intensive care unit with the severe COVID-19 outcome. Transcriptomic analysis revealed 1009 up-regulated and 501 down-regulated genes in the SARS group, with 10% of both being composed of long non-coding RNA. Ribosome and cell cycle pathways were enriched among down-regulated genes. The most connected proteins among the differentially expressed genes involved transport dysregulation, proteasome degradation, interferon response, cytokinesis failure, and host translation inhibition. Furthermore, interactome analysis showed Fibrillarin to be one of the key genes affected by SARS-CoV-2. This protein interacts directly with the N protein and long non-coding RNAs affecting transcription, translation, and ribosomal processes. This work reveals a group of dysregulated processes, including translation and cell cycle, as key pathways altered in severe COVID-19 outcomes.

MeSH

Cell Cycle, Work, Cells, Genes, Severe Acute Respiratory Syndrome, Rna, Untranslated, Rna, Long Noncoding, Covid-19, Sars-Cov-2

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