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

Abstract

AbstractSevere 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.