The PDZ domain of the E protein in SARS-CoV induces carcinogenesis and poor prognosis in LUAD

Microbes Infect. 2024 Nov-Dec;26(8):105381. doi: 10.1016/j.micinf.2024.105381. Epub 2024 Jun 22.

Abstract

Background: In both lung adenocarcinoma (LUAD) and severe acute respiratory syndrome (SARS), uncontrolled inflammation can be detected in lung tissue. The PDZ-binding motif (PBM) in the SARS-CoV-1 E protein has been demonstrated to be a virulence factor that induces a cytokine storm.

Methods: To identify gene expression fluctuations induced by PBM, microarray sequencing data of lung tissue infected with wild-type (SARS-CoV-1-E-wt) or recombinant virus (SARS-CoV-1-E-mutPBM) were analyzed, followed by functional enrichment analysis. To understand the role of the screened genes in LUAD, overall survival and immune correlation were calculated.

Results: A total of 12 genes might participate in the initial and developmental stages of LUAD through expression variation and mutation. Moreover, dysregulation of a total of 12 genes could lead to a poorer prognosis. In addition, the downregulation of MAMDC2 and ITGA8 by PBM could also affect patient prognosis. Although the conserved PBM (-D-L-L-V-) can be found at the end of the carboxyl terminus in multiple E proteins of coronaviruses, the specific function of each protein depends on the entire amino acid sequence.

Conclusions: In summary, PBM containing the SARS-CoV-1 E protein promoted the carcinogenesis of LUAD by dysregulating important gene expression profiles and subsequently influencing the immune response and overall prognosis.

Keywords: Bioinformatics; Envelope protein; LUAD; PBM; SARS-CoV-1.

MeSH terms

  • Adenocarcinoma of Lung / genetics
  • Adenocarcinoma of Lung / metabolism
  • Adenocarcinoma of Lung / mortality
  • Adenocarcinoma of Lung / pathology
  • Adenocarcinoma of Lung / virology
  • COVID-19 / genetics
  • COVID-19 / metabolism
  • COVID-19 / mortality
  • COVID-19 / virology
  • Carcinogenesis* / genetics
  • Coronavirus Envelope Proteins* / genetics
  • Coronavirus Envelope Proteins* / metabolism
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / virology
  • PDZ Domains*
  • Prognosis
  • SARS-CoV-2 / genetics
  • SARS-CoV-2 / pathogenicity
  • Severe acute respiratory syndrome-related coronavirus / genetics
  • Severe acute respiratory syndrome-related coronavirus / pathogenicity
  • Viroporin Proteins* / genetics
  • Viroporin Proteins* / metabolism

Substances

  • Coronavirus Envelope Proteins
  • Viroporin Proteins
  • E protein, SARS coronavirus