Dataset Information

Proteomic signature of host response to SARS-CoV-2 infection in the nasopharynx

ABSTRACT: Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2 infection has become a global health pandemic. COVID-19 severity ranges from asymptomatic infection to severe multi-organ disease. Although the inflammatory response has been implicated in the pathogenesis of COVID-19, the exact nature of dysregulation in signaling pathways has not yet been elucidated underscoring the need for further molecular characterization of SARS-CoV-2 infection in humans. Here, we characterize the host response directly at the point of viral entry through analysis of nasopharyngeal swabs. Multiplexed high resolution mass spectrometry-based proteomic analysis of confirmed COVID-19 cases and negative controls identified 7,682 proteins and revealed significant upregulation of interferon-mediated antiviral signaling in addition to multiple other proteins that are not interferon-stimulated genes (ISGs) or well-characterized during viral infections. Downregulation of several proteasomal subunits, E3 ubiquitin ligases, and components of protein synthesis machinery was significant upon SARS-CoV-2 infection. Targeted proteomics to measure abundance levels of MX1, ISG15, Stat1, RIG-I and CXCL10, permitted differentiation of COVID-19 positive from negative cases. Phosphoproteomic analysis revealed increased phosphorylation of several proteins with known antiviral properties and as well as several proteins including CEP131, CFAP57 and xxxx that have not previously been implicated in the context of viral (or coronavirus) infections. Additionally, decreased phosphorylation levels of AKT and PKC, which have been shown to play varying role in different viral infections, were observed in infected individuals relative to controls. These data provide novel insights that add depth to our understanding of SARS-CoV-2 infection in the upper airway and help characterize a signature for this viral infection.

INSTRUMENT(S): Orbitrap Eclipse, Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Nasopharynx

DISEASE(S): Covid-19

SUBMITTER: Akhilesh Pandey

LAB HEAD: Dr. Akhilesh Pandey

PROVIDER: PXD022889 | Pride | 2021-08-09

REPOSITORIES: Pride

ACCESS DATA

Similar Datasets

Project description:Objectives: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causes the worldwide COVID-19 pandemic. While SARS-CoV-2 can infect people of all ages and both sexes, senior populations are at greatest risk of severe disease and worse outcomes, and sexual dimorphism has been reported in COVID-19. COVID-19 causes damage to multiple organ systems, including the brain. Neurological symptoms are widely observed in patients with Covid-19, with many survivors suffering from persistent neurological impairment, potentially accelerating Alzheimer’s disease (AD). This study aims to investigate the mechanisms underlying the impact of age, and sex on neuroinflammation due to SARS-CoV-2 infection using mouse models. Methods: Wild-type C57BL/6 mice were subjected to intranasal inoculation of SARS-CoV-2 lineage B.1.351, followed by daily body weight monitoring. At 7 dpi, viral burden and inflammatory cytokine/chemokine responses in the lung and brain were determined by quantitative RT-PCR, followed by immunohistochemical and transcriptomic analyses. Results: Older age, male sex, showed increased lung viral loads and severity of SARS-CoV-2 infection in mice. No viral RNA was detected in the brains of infected mice; however, IL-6 and CCL2 mRNA increased significantly, particularly in brains of old and APOE4 mice. Unbiased brain RNA-seq/transcriptomic analysis showed that SARS-CoV-2 infection caused significant changes in gene expression profiles, and pathway analysis identified innate immunity and defense response to virus and other organisms as the major molecular networks affected in the brain by SARS-CoV-2 infection. Conclusions: Our findings demonstrate that age, and sex, modify the progression and outcome of SARS-CoV-2 infection. SARS-CoV-2 infection triggers neuroinflammatory responses despite the lack of detectable virus in the brain. Changes in molecular networks of innate immunity and defense response to microorganisms underlie the impact of SARS-CoV-2 infection in the brain. These findings in mice mimic epidemiological and clinical observations in humans with Covid-19.

Dataset Information

Proteomic signature of host response to SARS-CoV-2 infection in the nasopharynx

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure