Kinome and phosphoproteome reprogramming underlie the immunological abnormalities in severe COVID-19

ABSTRACT: The SARS-CoV-2 infection elicits widespread immunological reactions and causes severe diseases in some individuals. However, the molecular basis behind the excessive, yet non-productive immune response in COVID-19 patients with severe diseases is not fully understood. Nor is it fully known of the molecular and cellular discrepancies between severe COVID-19 and sepsis caused by other infections. To gain systems-level insights into the pathogenesis of COVID-19, we compared the blood proteome and phosphoproteome of patients under intensive care with or without SARS-CoV-2 infection, and healthy control subjects by quantitative mass spectrometry. SARS-CoV-2 infection causes global reprogramming of the kinome and the phosphoproteome, resulting in incomplete adaptive immune responses mediated by B cells and T cells, compromised innate immune response via inhibitory SIGLEC and SLAM family receptor signaling, and excessive JAK/STAT signaling. Our work identifies the kinases CK2, SYK, JAK2/3, TYK2, and the cytokine IL-12 as potential targets for the immunomodulatory treatment of severe COVID-19 and provides a valuable resource for deciphering the mechanism of pathogen-host interactions.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Cell, Blood

DISEASE(S): Severe Acute Respiratory Syndrome

SUBMITTER: Tomonori Kaneko  

LAB HEAD: Shawn SC Li

PROVIDER: PXD024087 | Pride | 2024-05-24

REPOSITORIES: Pride