Dataset Information

Proteomic and phosphoproteomic profiling of COVID-19-associated lung injury: a report based on rhesus macaques

ABSTRACT: Lung is the major organ affected by SARS-CoV-2. To explore the molecular mechanism in the lung after SARS-CoV-2 infection, we performed LC-MS based proteome and phosphoproteome analysis using lung tissue samples separated from rhesus macaques.

ORGANISM(S): Macaca Mulatta

SUBMITTER: Juntao Yang

PROVIDER: PXD027180 | iProX | Thu Jul 08 00:00:00 BST 2021

REPOSITORIES: iProX

ACCESS DATA

Publications

Proteomic and phosphoproteomic profiling of COVID-19-associated lung and liver injury: a report based on rhesus macaques.

Liu Jiang-Feng JF Zhou Ya-Nan YN Lu Shuai-Yao SY Yang Ye-Hong YH Wu Song-Feng SF Liu De-Pei DP Peng Xiao-Zhong XZ Yang Jun-Tao JT

Signal transduction and targeted therapy 20220128 1

PMID: 35091530

Similar Datasets

Project description:Inflammation following SARS-CoV-2 infection is a hallmark of COVID-19 and predictive of morbidity and death. However, the inflammatory pathways contributing to host-defense vs immune-mediated pathology have not been fully elucidated. This duality is clearly seen with type-I interferons (IFN-I) which are critical mediators of innate control of viral infections, but also drive recruitment of inflammatory cells to site of infection, a key feature of severe COVID-19. Here, we modulated IFN-I signaling in rhesus macaques (Macaca mulatta) prior to and during acute SARS-CoV-2 infection (day -1 through day 2 post infection) using a mutated IFNα2 (IFN-modulator; IFNmod) which blocks binding to IFNAR2 and signaling of endogenous IFN-I. IFNmod treatment resulted in a highly significant and consistent reduction in SARS-CoV-2 viral load in BAL, lung, and hilar LN (>3-log difference) and upper airways (nasal swabs). IFNmod also potently reduced inflammatory cytokines and chemokines in BAL, expansion of inflammatory monocytes (CD14+CD16+), and lung pathogenesis. Furthermore, Siglec-1 expression, which has been shown to enhance SARS-CoV-2 infection, was rapidly downregulated in the lung and on monocytes of IFNmod-treated SARS-CoV-2 infected RMs. Notably, while RNAseq analysis showed that IFNmod induced a modest upregulation of antiviral IFN-stimulated genes (ISGs) in uninfected RMs, it resulted in a robust reduction in pathways associated with both antiviral and inflammatory ISGs in SARS-CoV-2-infected RMs. In conclusion, IFNmod treatment provides sufficient levels of type I IFN signaling that inhibit viral replication while also limiting hyperinflammation. IFN-I plays a vital role in regulating SARS-CoV-2 replication, but uncontrolled IFN signaling has a detrimental impact on inflammation and pathogenesis. A better understanding of the role of IFN-I pathways is essential for designing therapies targeting these pathways and aimed at limiting COVID-19 pathogenesis.

Dataset Information

Proteomic and phosphoproteomic profiling of COVID-19-associated lung injury: a report based on rhesus macaques

Publications

Proteomic and phosphoproteomic profiling of COVID-19-associated lung and liver injury: a report based on rhesus macaques.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets