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SARS-CoV-2 proteins

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    SARS-CoV-2 spike PROTEIN protein induces brain pericyte immunoreactivity in absence of productive viral infection

    Authors: Rayan Khaddaj-Mallat; Natija Aldib; Anne-Sophie Paquette; Aymeric Ferreira; Sarah Lecordier; Maxime Bernard; Armen Saghatelyan; Ayman ElAli

    doi:10.1101/2021.04.30.442194 Date: 2021-05-03 Source: bioRxiv

    COVID-19 MESHD is a respiratory disease MESHD caused by severe acute respiratory syndrome coronavirus-2 MESHD (SARS-CoV-2). COVID-19 MESHD pathogenesis causes vascular-mediated neurological disorders MESHD via still elusive mechanisms. SARS-CoV-2 infects host MESHD cells by binding to angiotensin-converting enzyme 2 HGNC (ACE2), a transmembrane receptor that recognizes the viral spike (S) protein PROTEIN. Brain pericytes were recently shown to express ACE2 at the neurovascular interface, outlining their possible implication in microvasculature injury MESHD in COVID-19 MESHD. Yet, pericyte responses to SARS-CoV-2 is still to be fully elucidated. Using cell-based assays, we report that ACE2 HGNC expression in human brain vascular pericytes is highly dynamic and is increased upon S protein PROTEIN stimulation. Pericytes exposed to S protein PROTEIN underwent profound phenotypic changes translated by increased expression of contractile and myofibrogenic proteins, namely -smooth muscle actin (- SMA HGNC), fibronectin HGNC, collagen I, and neurogenic locus notch homolog protein-3 HGNC ( NOTCH3 HGNC). These changes were associated to an altered intracellular calcium (Ca2+) dynamic. Furthermore, S protein PROTEIN induced lipid peroxidation, oxidative and nitrosative stress in pericytes as well as triggered an immune reaction translated by activation of nuclear factor-kappa-B ( NF-{kappa}B HGNC) signalling pathway, which was potentiated by hypoxia MESHD, a condition associated to vascular comorbidities, which exacerbate COVID-19 MESHD pathogenesis. S protein PROTEIN exposure combined to hypoxia MESHD enhanced the production of pro-inflammatory cytokines involved in immune cell activation and trafficking, namely interleukin-8 HGNC ( IL-8 HGNC), IL-18 HGNC, macrophage migration inhibitory factor HGNC ( MIF HGNC), and stromal cell-derived factor-1 HGNC ( SDF-1 HGNC). Finally, we found that S protein PROTEIN could reach the mouse brain via the intranasal route and that reactive ACE2-expressing pericytes are recruited to the damaged tissue undergoing fibrotic scarring in a mouse model of cerebral multifocal micro-occlusions, a main reported vascular-mediated neurological condition associated to COVID-19 MESHD. Our data demonstrate that the released S protein PROTEIN is sufficient to mediate pericyte immunoreactivity, which may contribute to microvasculature injury MESHD in absence of a productive viral infection MESHD. Our study provides a better understanding for the possible mechanisms underlying cerebrovascular disorders MESHD in COVID-19 MESHD, paving the way to develop new therapeutic interventions.

    Potential role of aberrant mucosal immune response to SARS-CoV-2 in pathogenesis of IgA Nephropathy MESHD

    Authors: Zhao Zhang; Guorong Zhang; Meng Guo; Wanyin Tao; Xingzi Liu; Haiming Wei; Tengchuan Jin; Yuemiao Zhang; Shu Zhu

    doi:10.1101/2020.12.11.20247668 Date: 2020-12-11 Source: medRxiv

    Aberrant mucosal immunity has been suggested to play a pivotal role in pathogenesis of IgA nephropathy MESHD (IgAN), the most common form of glomerulonephritis MESHD worldwide. The outbreak of severe acute respiratory syndrome coronavirus (SARS-CoV-2) MESHD, the causal pathogen of coronavirus disease 2019 MESHD ( COVID-19 MESHD), has become a global concern. However, whether the mucosal immune response caused by SARS-CoV-2 influences the clinical manifestations of IgAN MESHD patients remains unknown. Here we tracked the SARS-CoV-2 anti-receptor binding domain (RBD) antibody levels in a cohort of 88 COVID-19 MESHD patients. We found that 52.3% of the COVID-19 MESHD patients produced more SARS-CoV-2 anti-RBD IgA than IgG or IgM, and the levels of the IgA were stable during 4-41 days of infection. Among these IgA-dominated COVID-19 MESHD patients, we found a severe COVID-19 MESHD patient concurrent with IgAN MESHD. The renal function of the patient declined presenting with increased serum creatinine during the infection and till 7 months post infection. This patient predominantly produced anti-RBD IgA as well as total IgA in the serum compared to that of healthy controls. The analysis of the IgA-coated microbiota as well as proinflammatory cytokine IL-18 HGNC, which was mainly produced in the intestine, reveals intestinal inflammation MESHD, although no obvious gastrointestinal symptom was reported. The mucosal immune responses in the lung are not evaluated due to the lack of samples from respiratory tract. Collectively, our work highlights the potential adverse effect of the mucosal immune response towards SARS-CoV-2, and additional care should be taken for COVID-19 MESHD patients with chronic diseases MESHD like IgAN.

    Outcome of SARS-CoV-2 infection MESHD linked to MAIT cell activation and cytotoxicity: evidence for an IL-18 HGNC dependent mechanism

    Authors: Héloïse Flament; Matthieu Rouland; Lucie Beaudoin; Amine Toubal; Léo Bertrand; Samuel Lebourgeois; Zouriatou Gouda; Camille Rousseau; Pauline Soulard; Maria Hurtado-Nedelec; Sandrine Luce; Karine Bailly; Muriel Andrieu; Christian Boitard; Anaïs Vallet-Pichard; Jean-Francois Gautier; Nadine Ajzenberg; Benjamin Terrier; Frédéric Pene; Jade Ghosn; Yazdan Yazdanpanah; Benoit Visseaux; Diane Descamps; Jean-Francois Timsit; Renato Costa Monteiro; Agnes Lehuen

    doi:10.1101/2020.08.31.20185082 Date: 2020-09-02 Source: medRxiv

    Immune system dysfunction MESHD is paramount in Coronavirus disease 2019 MESHD ( COVID-19 MESHD) severity and fatality rate. Mucosal-Associated Invariant T (MAIT) cells are innate-like T cells involved in mucosal immunity and protection against viral infections. Here, we studied the immune cell landscape, with emphasis on MAIT cells, in a cohort of 182 patients including patients at various stages of disease activity. A profound decrease of MAIT cell counts in blood of critically ill MESHD patients was observed. These cells showed a strongly activated and cytotoxic phenotype that positively correlated with circulating pro-inflammatory cytokines, notably IL-18 HGNC. MAIT cell alterations markedly correlated with disease severity and patient mortality. SARS-CoV-2-infected MESHD macrophages activated MAIT cells in a cytokine-dependent manner involving an IFN HGNC-dependent early phase and an IL-18 HGNC-induced later phase. Therefore, altered MAIT cell phenotypes represent valuable biomarkers of disease severity and their therapeutic manipulation might prevent the inflammatory phase involved in COVID-19 MESHD aggravation.

    Analysis of the intestinal microbiota in COVID-19 MESHD patients and its correlation with the inflammatory factor IL-18 HGNC and SARS-CoV-2-specific IgA

    Authors: Wanyin Tao; Shu Zhu; Guorong Zhang; Xiaofang Wang; Meng Guo; Weihong Zeng; Zihao Xu; Lianxin Liu; Kaiguang Zhang; Yucai Wang; Xiaoling Ma; Zhengxu Chen; Tengchuan Jin; Jianping Weng

    doi:10.1101/2020.08.12.20173781 Date: 2020-08-14 Source: medRxiv

    The current global COVID-19 pandemic MESHD COVID-19 pandemic MESHD is caused by beta coronavirus Severe Acute Respiratory Syndrome Coronavirus-2 MESHD (SARS-CoV-2), which already infected over 10 million and caused 500 thousand deaths by June 2020. Overproduction of cytokines triggered by COVID-19 MESHD infection, known as "cytokine storm", is a highly risk factor associated with disease severity. However, how COVID-19 MESHD infection induce cytokine storm is still largely unknown. Accumulating in vitro and in vivo evidence suggests that gut is also susceptible to COVID19 MESHD infection: Human intestinal organoids, an in vitro model which mimic the specific cell type and spatial structure of the intestine, were susceptible to SARS-CoV2 infection MESHD; A significant fraction of patients reported gut symptoms; Viral RNA may persist for more than 30 days and infectious virus could be isolated in fecal samples. The gastrointestinal tract is the primary site of interaction between the host immune system with symbiotic and pathogenic microorganisms. The bacteria resident in our gastrointestinal tract, known as gut microbiota, is important to maintain the homeostasis of our immune system. While imbalance of gut microbiota, or dysbiosis MESHD, is associated with multiple inflammation diseases5 MESHD. It's possible that SARS-CoV-2 infection MESHD may lead to alternation of gut microbiota thus worsen the host symptom. IL-18 HGNC is a proinflammatory cytokine produced multiple enteric cells, including intestinal epithelial cells (IECs), immune cells as well as enteric nervous system, and was shown to increase in the serum of COVID-19 MESHD patients. Immunoglobin A ( IgA HGNC) is mainly produced in the mucosal surfaces, in humans 40-60mg kg-1 day-1 than all other immunoglobulin isotypes combined, and at least 80% of all plasma cells are located in the intestinal lamina propria. Recent study showed that SARS-CoV-2 specific IgA HGNC in the serum is positively correlate with the disease severity in COVID-19 MESHD patients11. Here we investigated the alterations of microbiota in COVID-19 MESHD patients, and its correlation with inflammatory factor IL-18 HGNC and SARS-CoV2 specific IgA HGNC.

    Mapping Systemic Inflammation and Antibody Responses in Multisystem Inflammatory Syndrome in Children (MIS-C)

    Authors: Conor Gruber; Roosheel Patel; Rebecca Trachman; Lauren Lepow; Fatima Amanat; Florian Krammer; Karen M. Wilson; Kenan Onel; Daniel Geanon; Kevin Tuballes; Manishkumar Patel; Konstantinos Mouskas; Nicole Simons; Vanessa Barcessat; Diane Del Valle; Samantha Udondem; Gurpawan Kang; Sandeep Gangadharan; George Ofori-Amanfo; Adeeb Rahman; Seunghee Kim-Schulze; Alexander Charney; Sacha Gnjatic; Bruce Gelb; Miriam Merad; Dusan Bogunovic

    doi:10.1101/2020.07.04.20142752 Date: 2020-07-06 Source: medRxiv

    Initially, the global outbreak of COVID-19 MESHD caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spared children from severe disease. However, after the initial wave of infections, clusters of a novel hyperinflammatory disease MESHD have been reported in regions with ongoing SARS-CoV-2 MESHD epidemics. While the characteristic clinical features are becoming clear, the pathophysiology remains unknown. Herein, we report on the immune profiles of eight Multisystem Inflammatory Syndrome MESHD in Children ( MIS HGNC-C) cases. We document that all MIS HGNC-C patients had evidence of prior SARS-CoV-2 exposure, mounting an antibody response with normal isotype-switching and neutralization capability. We further profiled the secreted immune response by high-dimensional cytokine assays, which identified elevated signatures of inflammation MESHD ( IL-18 HGNC and IL-6 HGNC), lymphocytic and myeloid chemotaxis and activation ( CCL3 HGNC, CCL4 HGNC, and CDCP1 HGNC) and mucosal immune dysregulation ( IL-17A HGNC, CCL20 HGNC, CCL28 HGNC). Mass cytometry immunophenotyping of peripheral blood revealed reductions of mDC1 and non-classical monocytes, as well as both NK- and T- lymphocytes, suggesting extravasation to affected tissues. Markers of activated myeloid function were also evident, including upregulation of ICAM1 HGNC and FcR1 in neutrophil and non-classical monocytes, well-documented markers in autoinflammation MESHD and autoimmunity that indicate enhanced antigen presentation and Fc-mediated responses. Finally, to assess the role for autoimmunity secondary to infection, we profiled the auto-antigen reactivity of MIS HGNC-C plasma, which revealed both known disease-associated autoantibodies (anti-La) and novel candidates that recognize endothelial, gastrointestinal and immune-cell antigens. All patients were treated with anti- IL6R HGNC antibody or IVIG, which led to rapid disease resolution tracking with normalization of inflammatory markers.

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MeSH Disease
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