Global analysis of lysine acetylation in the brain cortex of K18-hACE2 mice infected with SARS-CoV-2

Proteomics. 2023 Aug;23(16):e2300096. doi: 10.1002/pmic.202300096. Epub 2023 Jun 13.

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected hundreds of millions of people all over the world and thus threatens human life. Clinical evidence shows that SARS-CoV-2 infection can cause several neurological consequences, but the existing antiviral drugs and vaccines have failed to stop its spread. Therefore, an understanding of the response to SARS-CoV-2 infection of hosts is vital to find a resultful therapy. Here, we employed a K18-hACE2 mouse infection model and LC-MS/MS to systematically evaluate the acetylomes of brain cortexes in the presence and absence of SARS-CoV-2 infection. Using a label-free strategy, 3829 lysine acetylation (Kac) sites in 1735 histone and nonhistone proteins were identified. Bioinformatics analyses indicated that SARS-CoV-2 infection might lead to neurological consequences via acetylation or deacetylation of important proteins. According to a previous study, we found 26 SARS-CoV-2 proteins interacted with 61 differentially expressed acetylated proteins with high confidence and identified one acetylated SARS-CoV-2 protein nucleocapsid phosphoprotein. We greatly expanded the known set of acetylated proteins and provide the first report of the brain cortex acetylome in this model and thus a theoretical basis for future research on the pathological mechanisms and therapies of neurological consequences after SARS-CoV-2 infection.

Keywords: #; K18-hACE2; SARS-CoV-2; brain cortex; lysine acetylation; neurological consequences.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Angiotensin-Converting Enzyme 2 / metabolism
  • Animals
  • Brain / metabolism
  • COVID-19* / pathology
  • Chromatography, Liquid
  • Disease Models, Animal
  • Humans
  • Lysine / metabolism
  • Mice
  • Mice, Transgenic
  • Peptidyl-Dipeptidase A / metabolism
  • SARS-CoV-2* / metabolism
  • Tandem Mass Spectrometry

Substances

  • Lysine
  • K-18 conjugate
  • Peptidyl-Dipeptidase A
  • Angiotensin-Converting Enzyme 2