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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

NSP8 (1)


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SARS-CoV-2 Proteins
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    Plasmacytoid dendritic cells produce type I interferon and reduce viral replication in airway epithelial cells after SARS-CoV-2 infection MESHD

    Authors: Luisa Cervantes-Barragan; Abigail Vanderheiden; Charlotte J Royer; Meredith E Davis-Gardner; Philipp Ralfs; Tatiana Chirkova; Larry J Anderson; Arash Grakoui; Mehul S Suthar

    doi:10.1101/2021.05.12.443948 Date: 2021-05-13 Source: bioRxiv

    Infection with SARS-CoV-2 has caused a pandemic of unprecedented dimensions. SARS-CoV-2 infects MESHD airway and lung cells causing viral pneumonia MESHD. The importance of type I interferon (IFN) HGNC production for the control of SARS-CoV-2 infection MESHD is highlighted by the increased severity of COVID-19 MESHD in patients with inborn errors of type I IFN MESHD response or auto-antibodies against IFN HGNC-. Plasmacytoid dendritic cells (pDCs) are a unique immune cell population specialized in recognizing and controlling viral infections through the production of high concentrations of type I IFN. In this study, we isolated pDCs from healthy donors and showed that pDCs are able to recognize SARS-CoV-2 and rapidly produce large amounts of type I IFN. Sensing of SARS-CoV-2 by pDCs was independent of viral replication since pDCs were also able to recognize UV-inactivated SARS-CoV-2 and produce type I IFN. Transcriptional profiling of SARS-CoV-2 and UV-SARS-CoV-2 stimulated pDCs also showed a rapid type I and III IFN response as well as induction of several chemokines, and the induction of apoptosis in pDCs. Moreover, we modeled SARS-CoV-2 infection MESHD in the lung using primary human airway epithelial cells (pHAEs) and showed that co-culture of pDCs with SARS-CoV-2 infected pHAEs MESHD induces an antiviral response and upregulation of antigen presentation in pHAE cells. Importantly, the presence of pDCs in the co-culture results in control of SARS-CoV-2 replication in pHAEs. Our study identifies pDCs as one of the key cells that can recognize SARS-CoV-2 infection MESHD, produce type I and III IFN and control viral replication in infected cells.

    Authors: Natalia G Sampaio; Lise Chauveau; Jonny Hertzog; Anne Bridgeman; Gerissa Fowler; Jurgen P Moonen; Maeva Dupont; Rebecca A Russel; Marko Noerenberg; Jan Rehwinkel

    doi:10.1101/2021.03.26.437180 Date: 2021-03-27 Source: bioRxiv

    Human cells respond to infection by SARS-CoV-2, the virus that causes COVID-19 MESHD, by producing cytokines including type I and III interferons (IFNs) and proinflammatory factors such as IL6 HGNC and TNF HGNC. IFNs can limit SARS-CoV-2 replication but cytokine imbalance contributes to severe COVID-19 MESHD. We studied how cells detect SARS-CoV-2 infection MESHD. We report that the cytosolic RNA sensor MDA5 HGNC was required for type I and III IFN induction in the lung cancer MESHD cell line Calu-3 upon SARS-CoV-2 infection MESHD. Type I and III IFN HGNC induction further required MAVS HGNC and IRF3 HGNC. In contrast, induction of IL6 HGNC and TNF HGNC was independent of the MDA5 HGNC- MAVS HGNC- IRF3 HGNC axis in this setting. We further found that SARS-CoV-2 infection MESHD inhibited the ability of cells to respond to IFNs. In sum, we identified MDA5 HGNC as a cellular sensor for SARS-CoV-2 infection MESHD that induced type I MESHD and III IFNs.

    Differential roles of RIG-I HGNC-like receptors in SARS-CoV-2 infection MESHD

    Authors: Duomeng Yang; Tingting Geng; Andrew G Harrison; PENGHUA WANG

    doi:10.1101/2021.02.10.430677 Date: 2021-02-11 Source: bioRxiv

    The retinoic acid-inducible gene I ( RIG-I HGNC) and melanoma MESHD melanoma HGNC differentiation-associated protein 5 ( MDA5 HGNC) are the major viral RNA sensors that are essential for activation of antiviral immune responses. However, their roles in severe acute respiratory syndrome MESHD (SARS)-causing coronavirus (CoV) infection MESHD are largely unknown. Herein we investigate their functions in human epithelial cells, the primary and initial target of SARS-CoV-2, and the first line of host defense. A deficiency in MDA5 HGNC ( MDA5 HGNC-/-), RIG-I HGNC or mitochondrial antiviral signaling protein HGNC ( MAVS HGNC) greatly enhanced viral replication. Expression of the type I/III interferons (IFN) HGNC was upregulated following infection in wild-type cells, while this upregulation was severely abolished in MDA5 HGNC-/- and MAVS HGNC-/-, but not in RIG-I HGNC-/- cells. Of note, ACE2 HGNC expression was ~2.5 fold higher in RIG-I HGNC-/- than WT cells. These data demonstrate a dominant role of MDA5 HGNC in activating the type I/III IFN response to SARS-CoV-2, and an IFN HGNC-independent anti-SARS-CoV-2 role of RIG-I HGNC.

    Successful Treatment of Convalescent Plasma Therapy in Three Patients With Severe SARS-CoV-2 Infection MESHD SARS-CoV-2 Infection MESHD in Fuzhou, China

    Authors: Di Wu; Xiaolin Zhu; Songjing Shi; Fenghui Lin; Baosong Xie; Guoxiang Lai; Lizhou Chen

    doi:10.21203/rs.3.rs-196885/v1 Date: 2021-02-01 Source: ResearchSquare

    Background Up to now, there is no specific treatment for coronavirus disease 2019 MESHD ( COVID-19 MESHD) yet except for general supportive care. Hence, it will be critical to find a new strategy for COVID-19 MESHD. The study is to explore whether convalescent plasma transfusion may be beneficial in the treatment of severe patients with COVID-19 MESHD.Methods This is a retrospective analysis of three severe patients with laboratory-confirmed COVID-19 MESHD and admitted in Fuzhou pulmonary hospital of Fujian province from February 18th, to May 15th,who met the following criteria: (1) within 3 weeks of symptom onset;laboratory confirmed cases or who had viremia MESHD conformed by clinical experts;(2)Severe patients with rapidly progress or the early stage of critically ill MESHD patients or who required plasma therapy were comprehensively evaluated by clinical experts. The data of clinical manifestations and the progresses of disease monitored by blood-gas analysis, biochemical tests, routine examine, radiological exam were abstracted and then analysis the changes before and after convalescent plasma transfusion. Results All three patients (one male and two females; age range, 57-65years) were treated with convalescent plasma during the study. Two patients had underlying chronic diseases MESHD, including diabetes MESHD and hypertension MESHD. The most common symptoms were fever MESHD (three cases, 3/3) and cough (two cases, 2/3). All patients were treated with a combination of two antiviral drugs (lopinaviritonavir or arbidol combined with IFN- HGNCɑ), whereas none of the patients were given glucocorticoids. Following plasma transfusion, the symptoms of the whole group improved to some degree, mainly manifested as reducing in coughing and body temperature normalized. Several parameters tended to improve as compared to pre-transfusion, including increased lymphocyte counts (0.97 × 109/L vs. 1.08 × 109/L) and decreased IL-6 HGNC (41.34 pg/ml vs. 13.83 pg/ml). The density of bilateral infiltration on CT imaging showed varying degrees of absorption within 7days. Throat swab nucleic acid test of most patients became negative for the novel coronavirus within 3 days after the transfusion. No adverse effects and severe complications were observed. Conclusions In this preliminary uncontrolled case series of 3severe patients with COVID-19 MESHD, convalescent plasma could be as a promising therapy for COVID-19 MESHD without corticosteroids and no serious adverse reactions associated with the transfusion of convalescent plasma were observed, which would improve the clinical outcomes following by improvement in their clinical status. Using the convalescent plasma at the early stage(less than 10 days) of disease could be more effective. Anticoagulation is necessary for severe patients with COVID-19 MESHD given the state of hypercoagulability MESHD. However, given the small sample size and limited study design, naturally these results should be taken with a grain of salt until replicated by other further investigation in larger well-controlled trials.

    Elevated temperature inhibits SARS-CoV-2 replication in respiratory epithelium independently of the induction of IFN HGNC-mediated innate immune defences

    Authors: Vanessa Herder; Kieran Dee; Joanna Wojtus; Daniel Goldfarb; Christoforos Rozario; Quan Gu; Ruth Jarrett; Ilaria Epifano; Andrew Stevenson; Steven McFarlane; Meredith Stewart; Agnieszka Szemiel; Rute Pinto; Andreu Masdefiol Garriga; Sheila Graham; Pablo Murcia; Chris Boutell; Elizabeth Williamson; William Hulme; Helen I McDonald; Laurie Tomlinson; Rohini Mathur; Henry Drysdale; Rosalind M Eggo; Kevin Wing; Angel Wong; Harriet Forbes; John Parry; Frank Hester; Sam Harper; Stephen JW Evans; Ian J Douglas; Liam Smeeth; Ben Goldacre

    doi:10.1101/2020.12.04.411389 Date: 2020-12-04 Source: bioRxiv

    The pandemic spread of SARS-CoV-2, the etiological agent of COVID-19 MESHD, represents a significant and ongoing international health crisis. A key symptom of SARS-CoV-2 infection MESHD is the onset of fever MESHD, with a hyperthermic temperature range of 38 to 41{degrees}C. Fever MESHD is an evolutionarily conserved host response to microbial infection MESHD and inflammation MESHD that can influence the outcome of viral pathogenicity and regulation of host innate and adaptive immune responses. However, it remains to be determined what effect elevated temperature has on SARS-CoV-2 tropism MESHD and replication. Utilizing a 3D air-liquid interface (ALI) model that closely mimics the natural tissue physiology and cellular tropism of SARS-CoV-2 infection MESHD in the respiratory airway, we identify tissue temperature to play an important role in the regulation of SARS-CoV-2 infection MESHD. We show that temperature elevation induces wide-spread transcriptome changes that impact upon the regulation of multiple pathways, including epigenetic regulation and lncRNA expression, without disruption of general cellular transcription or the induction of interferon ( IFN HGNC)-mediated antiviral immune defences. Respiratory tissue incubated at temperatures >37{degrees}C remained permissive to SARS-CoV-2 infection MESHD but severely restricted the initiation of viral transcription, leading to significantly reduced levels of intraepithelial viral RNA accumulation and apical shedding of infectious virus. To our knowledge, we present the first evidence that febrile temperatures associated with COVID-19 MESHD inhibit SARS-CoV-2 replication. Our data identify an important role for temperature elevation in the epithelial restriction of SARS-CoV-2 that occurs independently of the induction of canonical IFN HGNC-mediated antiviral immune defences and interferon-stimulated gene (ISG) expression.

    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.

    Suppression of MDA5 HGNC-mediated antiviral immune responses by NSP8 PROTEIN of SARS-CoV-2

    Authors: Ziwei Yang; Xiaolin Zhang; Fan Wang; Peihui Wang; Xiaojuan Li; Ersheng Kuang

    doi:10.1101/2020.08.12.247767 Date: 2020-08-12 Source: bioRxiv

    Melanoma differentiation-associated gene-5 HGNC ( MDA5 HGNC) acts as a cytoplasmic RNA sensor to detect viral dsRNA and mediates type I interferon ( IFN HGNC) signaling and antiviral innate immune responses to infection by RNA viruses. Upon recognition of viral dsRNA, MDA5 HGNC is activated with K63-linked polyubiquitination and then triggers the recruitment of MAVS HGNC and activation of TBK1 HGNC and IKK, subsequently leading to IRF3 HGNC and NF-{kappa}B HGNC phosphorylation. Great numbers of symptomatic and severe infections of SARS-CoV-2 MESHD are spreading worldwide, and the poor efficacy of treatment with type I interferon and antiviral agents indicates that SARS-CoV-2 escapes from antiviral immune responses via an unknown mechanism. Here, we report that SARS-CoV-2 nonstructural protein 8 ( NSP8 PROTEIN) acts as an innate immune suppressor and inhibits type I IFN signaling to promote infection of RNA viruses. It downregulates the expression of type I IFNs, IFN HGNC-stimulated genes and proinflammatory cytokines by binding to MDA5 HGNC and impairing its K63-linked polyubiquitination. Our findings reveal that NSP8 PROTEIN mediates innate immune evasion during SARS-CoV-2 infection MESHD and may serve as a potential target for future therapeutics for SARS-CoV-2 infectious diseases MESHD.

    COVID-19 MESHD: Role of the Interferons

    Authors: Claudio G. Gallo; Sirio Fiorino; Giovanni Posabella; Donato Antonacci; Antonio Tropeano; Emanuele Pausini; Carlotta Pausini; Tommaso Guarniero; Marco Zancanaro

    id:202008.0018/v1 Date: 2020-08-02 Source: Preprints.org

    COVID-19 MESHD disease, caused by the SARS-CoV2 virus, is a potentially fatal disease that represents a serious public health and economic problem worldwide. The SARS-CoV2 virus infects MESHD the lower respiratory tract and can cause pneumonia MESHD in humans. ARDS is the leading cause of death MESHD in COVID-19 MESHD disease. One of the main characteristics of ARDS is the cytokine storm, an uncontrolled systemic inflammatory response resulting from the release of pro-inflammatory cytokines and chemokines and growth factors, by immune cells. The other important aspect of the disease is represented by the involvement of the vascular organ that undergoes endothelitis. Hyperinflammation and endothelitis contribute in various ways to trigger coagulation disorders MESHD with diffuse micro thrombotic MESHD and thromboembolic MESHD phenomena. Lastly, multiple organ failure MESHD may occur (MOF). Since so far there is no approved treatment, there is an urgent need to reposition known treatments, considered safe, to be included in trials. Naturally produced interferons represent the body's first line of defense against viruses. Pharmacological forms, obtained by means of genetic recombination techniques, have long been approved and used to treat numerous pathologies. Interferons are divided into three families, within which some subfamilies are distinguishable. Only IFN-II comprises a single isoform which has completely different aspects and functions. The IFN I and III, however, each comprise different subfamilies (17 subfamilies the IFN-I and 4 subfamilies the IFN-III), share many aspects, representing the body's first antiviral response, but play different roles. The use of IFNs has been studied in two severe hCoV (Human Coronavirus) diseases, closely related to COVID-19 MESHD disease, such as SARS and MERS. Numerous in vitro and in vivo studies have been conducted, often in combination with other antivirals. The results have been controversial. The positive results in vitro and in experimental animals were often not replicable in humans. The possible positioning of these molecules in the right window of therapeutic opportunity requires that the complex dialogue between IFN HGNC, inflammasome, cytokines, pro-inflammatory chemokines, growth factors and barrier function be shed light.

    Early temporal dynamics of cellular responses to SARS-CoV-2

    Authors: Arinjay Banerjee; Patrick Budylowski; Daniel Richard; Hassaan Maan; Jennifer Aguiar; Nader El-Sayes; Benjamin J.-M. Tremblay; Sam Afkhami; Mehran Karimzadeh; Lily Yip; Mario A Ostrowski; Jeremy A Hirota; Robert Kozak; Terence D Capellini; Matthew S. Miller; Andrew G McArthur; Bo Wang; Andrew C Doxey; Samira Mubareka; Karen Mossman

    doi:10.1101/2020.06.18.158154 Date: 2020-06-18 Source: bioRxiv

    Two highly pathogenic human coronaviruses that cause severe acute respiratory syndrome MESHD (SARS) and Middle East respiratory syndrome MESHD ( MERS MESHD) have evolved proteins that can inhibit host antiviral responses, likely contributing to disease progression and high case-fatality rates. SARS-CoV-2 emerged in December 2019 resulting in a global pandemic. Recent studies have shown that SARS-CoV-2 is unable to induce a robust type I interferon (IFN) HGNC response in human cells, leading to speculation about the ability of SARS-CoV-2 to inhibit innate antiviral responses. However, innate antiviral responses are dynamic in nature and gene expression levels rapidly change within minutes to hours. In this study, we have performed a time series RNA-seq and selective immunoblot analysis of SARS-CoV-2 infected lung MESHD (Calu-3) cells to characterize early virus-host processes. SARS-CoV-2 infection MESHD upregulated transcripts for type I IFNs and interferon stimulated genes (ISGs) after 12 hours. Furthermore, we analyzed the ability of SARS-CoV-2 to inhibit type I IFN production and downstream antiviral signaling in human cells. Using exogenous stimuli, we discovered that SARS-CoV-2 is unable to modulate IFN{beta HGNC} production and downstream expression of ISGs, such as IRF7 HGNC and IFIT1 HGNC. Thus, data from our study indicate that SARS-CoV-2 may have evolved additional mechanisms, such as masking of viral nucleic acid sensing by host cells to mount a dampened innate antiviral response. Further studies are required to fully identify the range of immune-modulatory strategies of SARS-CoV-2. SignificanceHighly pathogenic coronaviruses that cause SARS and MERS have evolved proteins to shutdown antiviral responses. The emergence and rapid spread of SARS-CoV-2, along with its relatively low case-fatality rate have led to speculation about its ability to modulate antiviral responses. We show that SARS-CoV-2 is unable to block antiviral responses that are mounted by exogenous stimuli. Data from our study provide promising support for the use of recombinant type I IFN as combination therapy to treat COVID-19 MESHD patients. Furthermore, our data also suggest that the inability of SARS-CoV-2 to efficiently modulate antiviral responses may be associated with its low case-fatality rate compared to other pathogenic CoVs that cause SARS and MERS.

    The Zinc Finger Antiviral Protein restricts SARS-CoV-2

    Authors: Rayhane Nchioua; Janis Mueller; Carina Conzelmann; Ruediger Gross; Steffen Stenger; Daniel Sauter; Jan Muench; Konstantin MJ Sparrer; Frank Kirchhoff

    doi:10.1101/2020.06.04.134379 Date: 2020-06-04 Source: bioRxiv

    Recent evidence shows that the Severe Acute Respiratory Syndrome Coronavirus 2 MESHD (SARS-CoV-2) is highly sensitive to interferons (IFNs). However, the underlying antiviral effectors remain to be defined. Here, we show that Zinc finger antiviral protein ( ZAP HGNC) that specifically targets CpG dinucleotides in viral RNA sequences restricts SARS-CoV-2. We demonstrate that ZAP HGNC and its cofactors KHNYN HGNC and TRIM25 HGNC are expressed in human lung cells. Type I, II and III IFNs all strongly inhibited SARS-CoV-2 and further induced ZAP HGNC expression. Strikingly, SARS-CoV-2 and its closest relatives from bats show the strongest CpG suppression among all known human and bat coronaviruses, respectively. Nevertheless, knock-down of ZAP HGNC significantly increased SARS-CoV-2 production in lung cells, particularly upon treatment with IFN- HGNC or IFN-{gamma HGNC}. Thus, our results identify ZAP HGNC as an effector of the IFN response against SARS-CoV-2, although this pandemic pathogen may be preadapted to the low CpG environment in humans. HighlightsO_LISARS-CoV-2 and its closest bat relatives show strong CpG suppression C_LIO_LIIFN-{beta}, -{gamma} and -{lambda} inhibit SARS-CoV-2 with high efficiency C_LIO_LIZAP restricts SARS-CoV-2 and contributes to the antiviral effect of IFNs C_LI

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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