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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (7)


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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.

    Smoking modulates different secretory subpopulations expressing SARS-CoV-2 entry genes in the nasal and bronchial airways

    Authors: Ke Xu; Xingyi Shi; Chris Husted; Rui Hong; Yichen Wang; Boting Ning; Travis Sullivan; Kimberly M Rieger-Christ; Fenghai Duan; Helga Marques; Adam C Gower; Xiaohui Xiao; Hanqiao Liu; Gang Liu; Grant Duclos; Avrum Spira; Sarah A Mazzilli; Ehab Billatos; Marc E Lenburg; Joshua D Campbell; Jennifer Beane

    doi:10.1101/2021.03.30.21254564 Date: 2021-04-04 Source: medRxiv

    Coronavirus Disease 2019 MESHD ( COVID-19 MESHD) is caused by severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2), which infects host cells with help from the Viral Entry (VE) proteins ACE2 HGNC, TMPRSS2 HGNC, and CTSL HGNC. Proposed risk factors for viral infection MESHD, as well as the rate of disease progression, include age, sex, chronic obstructive pulmonary disease MESHD, cancer MESHD, and cigarette smoking. To investigate whether the proposed risk factors increase viral infection MESHD by modulation of the VE genes, we examined gene expression profiles of 796 nasal and 1,673 bronchial samples across four lung cancer MESHD screening cohorts containing individuals without COVID-19 MESHD. Smoking was the only clinical factor reproducibly associated with the expression of any VE gene across cohorts. ACE2 HGNC expression was significantly up-regulated with smoking in the bronchus but significantly down-regulated with smoking in the nose. Furthermore, expression of individual VE genes were not correlated between paired nasal and bronchial samples from the same patients. Single-cell RNA-seq of nasal brushings revealed that an ACE2 HGNC gene module was detected in a variety of nasal secretory cells with the highest expression in the C15orf48 HGNC+ secretory cells, while a TMPRSS2 HGNC gene module was most highly expressed in nasal keratinizing epithelial cells. In contrast, single-cell RNA-seq of bronchial brushings revealed that ACE2 HGNC and TMPRSS2 HGNC gene modules were most enriched in MUC5AC HGNC+ bronchial goblet cells. The CTSL HGNC gene module was highly expressed in immune populations of both nasal and bronchial brushings. Deconvolution of bulk RNA-seq showed that the proportion of MUC5AC HGNC+ goblet cells was increased in current smokers in both the nose and bronchus but proportions of nasal keratinizing epithelial cells, C15orf48 HGNC+ secretory cells, and immune cells were not associated with smoking status. The complex association between VE gene expression and smoking in the nasal and bronchial epithelium revealed by our results may partially explain conflicting reports on the association between smoking and SARS-CoV-2 infection MESHD.

    Differential gene expression by RNA-Seq in Sigma-2 Receptor/ TMEM97 HGNC knockout cells reveals its role in complement activation and SARS-CoV-2 viral uptake

    Authors:

    doi:10.1101/2021.03.14.435180 Date: 2021-03-15 Source: bioRxiv

    Our lab has recently shown that the Sigma-2 Receptor/Transmembrane Protein 97 (sigma- 2R/ TMEM97 HGNC) interacts with the low-density lipoprotein receptor HGNC ( LDLR HGNC) and facilitates the enhanced uptake of various ligands including lipoproteins and intrinsically disordered proteins. TMEM97 HGNC has been recently been shown to interact with severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) viral proteins, highlighting its potential involvement with viral entry into the cell. We hypothesized that sigma-2R/ TMEM97 HGNC may play a role in facilitating viral uptake, and with the regulation of inflammatory and thrombotic MESHD pathways that are involved with viral infection MESHD. In this study, we identified the top differentially expressed genes upon the knockout of sigma-2R/ TMEM97 HGNC, and analyzed the genes involved with the inflammatory and thrombotic MESHD cascades, effects that are observed in patients infected with SARS-CoV-2. We found that the ablation of sigma-2R/ TMEM97 HGNC resulted in an increase in Complement Component MESHD 4 Binding Protein ( C4BP HGNC) proteins, at both the translational and transcriptional levels. We also showed that sigma-2R/ TMEM97 HGNC interacts with the cellular receptor for SARS-CoV-2, the human angiotensin-converting enzyme 2 HGNC ( ACE2 HGNC) receptor, forming a protein complex, and that disruption of this complex results in the inhibition of viral uptake. The results of this study suggest that sigma-2R/ TMEM97 HGNC may be a novel therapeutic target to inhibit SARS- CoV-2 viral uptake, as well as to decrease inflammatory and thrombotic MESHD effects through the modulation of the complement cascade.

    Sensing of cytoplasmic chromatin by cGAS activates innate immune response in SARS-CoV-2 infection MESHD

    Authors: Zhuo Zhou; Xinyi Zhang; Xiaobo Lei; Xia Xiao; Tao Jiao; Ruiyi Ma; Xiaojing Dong; Qi Jiang; Wenjing Wang; Yujin Shi; Tian Zheng; Yuting Tan; Zichun Xiang; Lili Ren; Tao Deng; Zhengfan Jiang; Zhixun Dou; Wensheng Wei; Jianwei Wang

    doi:10.21203/rs.3.rs-235742/v1 Date: 2021-02-12 Source: ResearchSquare

    The global coronavirus disease 2019 MESHD ( COVID-19 MESHD) pandemic is caused by severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2), a positive-sense RNA virus. How the host immune system senses and responds to SARS-CoV-2 infection MESHD remain to be determined. Here, we report that SARS-CoV-2 infection MESHD activates the innate immune response through the cytosolic DNA sensing cGAS-STING pathway. SARS-CoV-2 infection MESHD induces the cellular level of 2'3'-cGAMP associated with STING activation. cGAS recognizes chromatin DNA shuttled from the nucleus as a result of cell-to-cell fusion upon SARS-CoV-2 infection MESHD. We further demonstrate that the expression of spike protein PROTEIN from SARS-CoV-2 and ACE2 HGNC from host cells is sufficient to trigger cytoplasmic chromatin upon cell fusion. Furthermore, cytoplasmic chromatin-cGAS-STING pathway, but not MAVS HGNC mediated viral RNA sensing pathway, contributes to interferon and pro-inflammatory gene expression upon cell fusion. Finally, we show that cGAS is required for host antiviral responses against SARS-CoV-2, and a STING-activating compound potently inhibits viral replication. Together, our study reported a previously unappreciated mechanism by which the host innate immune system responds to SARS-CoV-2 infection MESHD, mediated by cytoplasmic chromatin from the infected cells. Targeting the cytoplasmic chromatin-cGAS-STING pathway may offer novel therapeutic opportunities in treating COVID-19 MESHD. In addition, these findings extend our knowledge in host defense against viral infection MESHD by showing that host cells’ self-nucleic acids can be employed as a “danger signal” to alarm the immune system.

    GRP78 HGNC binds SARS-CoV-2 Spike PROTEIN SARS-CoV-2 Spike MESHD protein and ACE2 HGNC and GRP78 HGNC depleting antibody blocks viral entry and infection in vitro

    Authors: Anthony J Carlos; Dat P Ha; Da-Wei Yeh; Richard Van Krieken; Parkash Gill; Keigo Machida; Amy Lee; Faisal M Al Ahbabi; Yasser S Mohammed; Nasser M Al Falasi; Noor M Almheiri; Sumaya M Al Blooshi; Quentin Muzzin; Loic Desquilbet; Larissa Thackray; Michael D Diamond; James E. Crowe

    doi:10.1101/2021.01.20.427368 Date: 2021-01-20 Source: bioRxiv

    The severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2), the causative agent of the current COVID-19 MESHD global pandemic, utilizes the host receptor angiotensin-converting enzyme 2 ( ACE2 HGNC) for viral entry. However, other host factors may also play major roles in viral infection MESHD. Here we report that the stress-inducible molecular chaperone GRP78 HGNC can form a complex with the SARS-CoV-2 Spike PROTEIN SARS-CoV-2 Spike MESHD protein and ACE2 HGNC intracellularly and on the cell surface, and that the substrate binding domain of GRP78 HGNC is critical for this function. Knock-down of GRP78 HGNC by siRNA dramatically reduced cell surface ACE2 HGNC expression. Treatment of lung epithelial cells with a humanized monoclonal antibody (hMAb159), selected for its ability to cause GRP78 HGNC endocytosis and its safe clinical profile in preclinical models, reduces cell surface ACE2 HGNC expression, SARS-CoV-2 Spike PROTEIN-driven viral entry, and significantly inhibits SARS-CoV-2 infection MESHD in vitro. Our data suggest that GRP78 HGNC is an important host auxiliary factor for SARS-CoV-2 entry and infection MESHD and a potential target to combat this novel pathogen and other viruses that utilize GRP78 HGNC.

    Modeling COVID-19 MESHD with Human Pluripotent Stem Cell-Derived Cells Reveals Synergistic Effects of Anti-inflammatory Macrophages with ACE2 HGNC Inhibition Against SARS-CoV-2

    Authors: Fuyu Duan; Liyan Guo; Liuliu Yang; Yuling Han; Abhimanyu Thakur; Benjamin E. Nilsson-Payant; Pengfei Wang; Zhao Zhang; Chui Yan Ma; Xiaoya Zhou; Teng Han; Tuo Zhang; Xing Wang; Dong Xu; Xiaohua Duan; Jenny Xiang; Hung-fat Tse; Can Liao; Weiren Luo; Fang-Ping Huang; Ya-Wen Chen; Todd Evans; Robert E. Schwartz; Benjamin tenOever; David D. Ho; Shuibing Chen; Jie Na; Qizhou Lian; Huanhuan Joyce Chen

    doi:10.21203/rs.3.rs-62758/v2 Date: 2020-08-20 Source: ResearchSquare

    Dysfunctional immune responses contribute critically to the progression of Coronavirus Disease MESHD-2019 ( COVID-19 MESHD) from mild to severe stages including fatality, with pro-inflammatory macrophages as one of the main mediators of lung hyper-inflammation MESHD. Therefore, there is an urgent need to better understand the interactions among SARS-CoV-2 permissive cells, macrophage, and the SARS-CoV-2 virus, thereby offering important insights into new therapeutic strategies.  Here, we used directed differentiation of human pluripotent stem cells (hPSCs) to establish a lung and macrophage co-culture system and model the host-pathogen interaction and immune response caused by SARS-CoV-2 infection MESHD. Among the hPSC-derived lung cells, alveolar type II MESHD and ciliated cells are the major cell populations expressing the viral receptor ACE2 HGNC and co-effector TMPRSS2 HGNC, and both were highly permissive to viral infection MESHD. We found that alternatively polarized macrophages (M2) and classically polarized macrophages (M1) had similar inhibitory effects on SARS-CoV-2 infection MESHD. However, only M1 macrophages significantly up-regulated inflammatory factors including IL-6 HGNC and IL-18 HGNC, inhibiting growth and enhancing apoptosis of lung cells. Inhibiting viral entry into target cells using an ACE2 HGNC blocking antibody enhanced the activity of M2 macrophages, resulting in nearly complete clearance of virus and protection of lung cells. These results suggest a potential therapeutic strategy, in that by blocking viral entrance to target cells while boosting anti-inflammatory action of macrophages at an early stage of infection, M2 macrophages can eliminate SARS-CoV-2, while sparing lung cells and suppressing the dysfunctional hyper MESHD-inflammatory response mediated by M1 macrophages.    

    Type 1 diabetes onset triggered by COVID-19 MESHD

    Authors: Lucien Marchand; Matthieu Pecquet; Cédric Luyton

    doi:10.21203/rs.3.rs-38116/v1 Date: 2020-06-27 Source: ResearchSquare

    The epidemic of coronavirus disease-2019 ( COVID-19 MESHD) is caused by the severe acute respiratory syndrome-coronavirus-2 MESHD (SARS-CoV-2) virus. Some data describing characteristics and prognosis of patients with COVID-19 MESHD and diabetes MESHD are now available, for example for hospitalized patients in the CORONADO study. Potential links between diabetes MESHD and COVID-19 MESHD infection were already described. Indeed Angiotensin-converting-enzyme 2 HGNC ( ACE2 HGNC) has been identified as the receptor for the coronavirus spike protein PROTEIN, and ACE HGNC is expressed on pancreatic beta cells. It was suggested that SARS-CoV2 could induce beta cell damage and new onset diabetes MESHD, but the phenotype of these new cases of diabetes MESHD has not been described.This observation presented in that paper highlights the fact that COVID-19 MESHD infection may also trigger type 1 diabetes MESHD onset. Viral infection MESHD, in particular by enteroviruses but also by coronaviruses, is a well-known environmental trigger for the development of type 1 diabetes MESHD. In the case presented herein, there was a short delay between COVID-19 MESHD infection and diabetes MESHD onset. It remains to determine if the hyperinflammation/cytokine storm described with this infection could accelerate the onset of type 1 diabetes MESHD in genetically susceptible individuals.The relationship between SARS-CoV2 exposition and autoimmune diabetes MESHD development must be further studied, and incidence of type 1 diabetes MESHD will be carefully observed in the next months.

    Novel ACE2 HGNC-Independent Carbohydrate-Binding of SARS-CoV-2 Spike PROTEIN Protein to Host Lectins and Lung Microbiota

    Authors: Fabrizio Chiodo; Sven C.M Bruijns; Ernesto Rodriguez; R.J. Eveline Li; Antonio Molinaro; Alba Silipo; Flaviana Di Lorenzo; Dagmar Garcia-Rivera; Yury Valdes-Balbin; Vicente Verez-Bencomo; Yvette van Kooyk

    doi:10.1101/2020.05.13.092478 Date: 2020-05-14 Source: bioRxiv

    The immediate call for translational research in the field of coronavirus disease MESHD ( COVID-19 MESHD) pandemic, needs new and unexplored angles to support and contribute to this important worldwide health problem. The aim of this study is to better understand the pathogenic mechanisms underlying COVID-19 MESHD, deciphering the carbohydrate-mediated interactions of the SARS-CoV-2 spike PROTEIN protein. We studied the carbohydrate-binding receptors that could be important for viral entry and for immune-modulatory responses, and we studied the interactions of the spike protein PROTEIN with the host lung microbiota. Exploring solid-phase immunoassays, we evaluated the interactions between the SARS-CoV-2 spike PROTEIN protein and a library of 12 different human carbohydrate-binding proteins (C-type lectins and Siglecs) involved in binding, triggering and modulation of innate and adaptive immune-responses. We revealed a specific binding of the SARS-CoV-2 spike PROTEIN protein to the receptors DC-SIGN, MGL HGNC, Siglec-9 HGNC and Siglec-10 HGNC that are all expressed on myeloid immune cells. In addition, because the lung microbiota can promote or modulate viral infection, we studied the interactions between the SARS-CoV-2 spike PROTEIN protein and a library of Streptococcus pneumoniae capsular polysaccharides, as well as other bacterial glyco-conjugates. We show specific binding of the spike protein PROTEIN to different S. pneumoniae capsular polysaccharides (serotypes 19F and 23F but not to serotype 14). Moreover we demonstrated a specific binding of SARS-CoV-2 spike PROTEIN protein to the lipopolysaccharide from the opportunistic human pathogen Pseudomonas aeruginosa, one of the leading cause of acute nosocomial infections MESHD and pneumonia MESHD. Interestingly, we identified rhamnosylated epitopes as one of the discriminating structures in lung microbiota to bind SARS-CoV-2 spike PROTEIN protein. In conclusion, we revealed novel ACE2 HGNC-independent carbohydrate-mediated interactions with immune modulating lectins expressed on myeloid cells, as well as host lung microbiota glyco-conjugates. Our results identified new molecular pathways using host lectins and signalling, that may contribute to viral infection MESHD and subsequent immune exacerbation. Moreover we identified specific rhamnosylated epitopes in lung microbiota to bind SARS-CoV-2, providing a hypothetical link between the presence of specific lung microbiota and SARS-CoV-2 infection MESHD and severity.

    The landscape of host genetic factors involved in infection to common viruses and SARS-CoV-2

    Authors: Linda Kachuri; Stephen S Francis; Maike Morrison; George Wendt; Yohan Bossé; Taylor B Cavazos; Sara R Rashkin; Elad Ziv; John S Witte

    doi:10.1101/2020.05.01.20088054 Date: 2020-05-07 Source: medRxiv

    Introduction: Humans and viruses have co-evolved for millennia resulting in a complex host genetic architecture. Understanding the genetic mechanisms of immune response to viral infection provides insight into disease etiology and informs public health interventions. Methods: We conducted a comprehensive study linking germline genetic variation and gene expression with antibody response to 28 antigens for 16 viruses using serological data from 7924 participants in the UK Biobank cohort. Using test results from 2010 UK Biobank subjects, we also investigated genetic determinants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection MESHD. Results: Signals in human leukocyte antigen (HLA) class II region dominated the landscape of viral antibody response, with 40 independent loci and 14 independent classical alleles, 7 of which exhibited pleiotropic effects across viral families. Genome-wide association analyses discovered 7 novel genetic loci associated with viral antibody response (P<5.0x10-8), including FUT2 (19q13.33) for human polyomavirus BK (BKV), STING1 (5q31.2) for Merkel cell polyomavirus (MCV), as well as CXCR5 (11q23.3) and TBKBP1 (17q21.32) for human herpesvirus 7. Transcriptome-wide association analyses identified 114 genes associated with response to viral infection MESHD, 12 outside of the HLA region, including ECSCR: P=5.0x10-15 (MCV), NTN5 HGNC: P=1.1x10-9 (BKV), and P2RY13 HGNC: P=1.1x10-8 (Epstein-Barr virus nuclear antigen). We also demonstrated pleiotropy between viral response genes and complex diseases, such as C4A expression in varicella zoster virus and schizophrenia MESHD. Finally, our analyses of SARS-CoV-2 revealed the first genome-wide significant infection susceptibility signal in EHF, an epithelial-specific transcriptional repressor implicated in airway disease. Targeted analyses of expression quantitative trait loci suggest a possible role for tissue-specific ACE2 HGNC expression in modifying SARS-CoV-2 susceptibility. Conclusions: Our study confirms the importance of the HLA region in host response to viral infection MESHD and elucidates novel genetic determinants of host-virus interaction. Our results may have implications for complex disease etiology and COVID-19 MESHD.

    Identification of Drugs Blocking SARS-CoV-2 Infection MESHD using Human Pluripotent Stem Cell-derived Colonic Organoids

    Authors: Xiaohua Duan; Yuling Han; Liuliu Yang; Benjamin Nilsson; Pengfei Wang; Tuo Zhang; Xing Wang; Dong Xu; Jenny Zhaoying Xiang; skyler uhl; Yaoxing Huang; Huanhuan Chen; Hui Wang; Benjamin R. tenOever; Robert E. Schwartz; David D Ho; Fong Cheng Pan; Shuibing Chen; Todd R. Evans

    doi:10.1101/2020.05.02.073320 Date: 2020-05-02 Source: bioRxiv

    Summary ParagraphThe current COVID-19 pandemic MESHD COVID-19 pandemic MESHD is caused by SARS-coronavirus MESHD 2 (SARS-CoV-2). There are currently no therapeutic options for mitigating this disease due to lack of a vaccine and limited knowledge of SARS-CoV-2 biology. As a result, there is an urgent need to create new disease models to study SARS-CoV-2 biology and to screen for therapeutics using human disease-relevant tissues. COVID-19 MESHD patients typically present with respiratory symptoms including cough, dyspnea MESHD, and respiratory distress, but nearly 25% of patients have gastrointestinal indications including anorexia MESHD, diarrhea MESHD, vomiting MESHD, and abdominal pain MESHD. Moreover, these symptoms are associated with worse COVID-19 MESHD outcomes1. Here, we report using human pluripotent stem cell-derived colonic MESHD organoids (hPSC-COs) to explore the permissiveness of colonic cell types to SARS-CoV-2 infection MESHD. Single cell RNA-seq and immunostaining showed that the putative viral entry receptor ACE2 HGNC is expressed in multiple hESC-derived colonic cell types, but highly enriched in enterocytes. Multiple cell types in the COs can be infected by a SARS-CoV-2 pseudo-entry virus, which was further validated in vivo using a humanized mouse model. We used hPSC-derived COs in a high throughput platform to screen 1280 FDA-approved drugs against viral infection MESHD. Mycophenolic acid and quinacrine dihydrochloride were found to block the infection of SARS-CoV-2 pseudo-entry virus in COs both in vitro and in vivo, and confirmed to block infection of SARS-CoV-2 MESHD virus. This study established both in vitro and in vivo organoid models to investigate infection of SARS-CoV-2 disease MESHD-relevant human colonic cell types and identified drugs that blocks SARS-CoV-2 infection MESHD, suitable for rapid clinical testing.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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