Dataset Information

SARS-COV-2 Uses CD4 to infect T Helper Lymphocytes

ABSTRACT: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or CoV-2) is the agent of a major global outbreak of respiratory tract disease known as COVID-19. CoV-2 infects the lungs and may cause several immune-related complications such as lymphocytopenia and cytokine storm which are associated with the severity of the disease and predict mortality. The mechanism by which CoV-2 infection may result in immune system dysfunction is not fully understood. Here we showed that CoV-2 infects human CD4+ T helper cells, but not CD8+ T cells. CoV-2 is found in the blood and bronchoalveolar lavage T helper cells of severe COVID-19 patients. We demonstrated that CoV-2 spike glycoprotein (S) (sCoV-2) directly binds to the CD4 co-receptor, which in turn mediates the entry of CoV-2 in T helper cells in a mechanism that also requires ACE2 and TMPRSS2. Once inside T helper cells, CoV-2 assembles viral factories, impairs cell function and may cause cell death. CoV-2 infected T helper cells express higher amounts of IL-10, which has been associated with viral persistence and disease severity. Thus, CD4-mediated CoV-2 infection of T helper cells may explain the poor adaptive immune response of many COVID-19 patients.

INSTRUMENT(S): Synapt MS

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): T Cell, Blood

DISEASE(S): Covid-19

SUBMITTER: Victor Corasolla Carregari

LAB HEAD: Daniel Martins-de-Souza

PROVIDER: PXD020967 | Pride | 2023-07-28

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	TCell_Covid_T2_2.rar	Other
	TCell_PrideSubmission.DerivedFromSearch9d40b6ff-1f3f-4520-b4bf-f3f562a0a751.mgf	Mgf
	TCell_PrideSubmission.csv	Csv
	TCell_PrideSubmission.mzid.gz	Mzid

Items per page:

1 - 4 of 4

Similar Datasets

Project description:Background. COVID-19-induced neurological disease is a growing concern. Here we provide a comprehensive clinical, molecular, and neuroimaging investigation of patients presenting neurological symptoms to investigate underlying processes. Methods. We performed a detailed systematized clinical, laboratory, and neuroimaging (CT/MRI) data analysis from 35 mild to severe Brazilian COVID-19 hospitalised patients with clinical indications for cerebrospinal fluid (CSF) exam. In patients' CSF, we measured interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-α) and the Alzheimer's disease-associated biomarkers amyloid-beta (Aβ)1-40, Aβ1-42, Tau and pTau181 levels (n=31-35). In addition, CSF proteomics and the search for SARS-CoV-2 spike protein presence using shotgun and targeted multiple reaction monitoring liquid-chromatography/mass-spectrometry were performed (n=16). We further evaluated a 29-cytokine panel in patients’ blood (n=16). An electronic questionnaire was conducted one-year post-hospitalisation (n=19, 63.3%). Findings. COVID-19 patients presented heterogeneous clinical and neurological features, including encephalopathy, encephalitis, and neuromuscular syndromes, despite low pulmonary burden. Patients showed increased circulating cytokines and CSF IL-6 and TNF-α levels compared to controls. Alzheimer’s disease-related biomarkers were unaltered compared to controls. COVID-19 altered CSF proteomic pathways associated to complement and coagulation cascades, immune-inflammatory, metabolism and amyloidosis. We found no traces of spike protein in patients’ CSF. Severe patients presented more pronounced neuroimaging alterations, altered CSF levels of IL-6, Tau, and Aβ-species compared to mild patients. Peripheral inflammation markers correlated with CSF IL-6 and Tau-species levels. Finally, in a one-year post-COVID survey, survivors were not recovered entirely (12/19) and reported confusion or memory/attention deficits (13/19). Interpretation. COVID-19 induces a broad spectrum of neurological presentations associated with changes in central nervous system (CNS) inflammatory and neurodegenerative molecular and structural biomarkers that correlate with systemic inflammation and disease severity. Given that neurological symptoms persist up to one-year post-COVID, our results urge us to investigate whether systemic, and CNS molecular changes are permanent or alleviated so that COVID-19 patients with lingering symptoms are adequately treated.

Project description:Coronaviruses belong to a well-known family of enveloped RNA viruses and the causative agent of the common cold. Although the seasonal coronaviruses do not pose a threat to human life, three members of this family, i.e., SARS-CoV, MERS-CoV and recently, SARS-CoV2, may cause severe acute respiratory syndrome that may lead to death. Unfortunately, COVID-19 has already caused more than 4,4 million deaths worldwide. Although much is better understood about the immunopathogenesis of the lung disease, important information about systemic disease is still missing, mainly concerning neurological parameters. In this context, we sought to evaluate immunometabolic changes using in vitro and in vivo models of hamsters infected with SARS-CoV2. Here show that, besides infecting and replicating in glial cells, SARS-CoV2 induces important changes in protein expression and metabolic pathways, specially involved in carbon metabolism, glycolysis, and mitochondrial respiration. Interestingly, many of the differentially expressed proteins during SARS-CoV2 infection overlapped with proteins correlated with neurological diseases, such as Parkinsons's Disease, multiple sclerosis, amyotrophic lateral sclerosis and Huntington's disease. Metabolic analysis by high resolution real-time respirometry evidenced hyperactivation of glycolysis and mitochondrial respiration, which was confirmed by metabolomics. Brain infection with SARS-CoV2 was confirmed in vivo as hippocampus, cortex and olfactory bulb of infected hamsters were positive for viral genome both at 4 and 7 days post-infection. Unexpectedly, we observed that glutamine was significantly reduced in mixed glial cells infected with SARS-CoV2 and that the blockade of glutaminolysis significantly reduced viral replication and pro-inflammatory response. Altogether, our data confirms the infection of brain cells by SARS-CoV2 but, most importantly, there is an important change in overall protein expression profile, mostly of proteins related to metabolic pathways. This may suggest that some of the neurological impairments observed during COVID-19, as the brain fog and cognitive impairment, may rely on altered protein expression and unbalanced glutamine/glutamate levels, whose importance for adequate brain function is unquestionable.

Dataset Information

SARS-COV-2 Uses CD4 to infect T Helper Lymphocytes

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets