Establishing Cellular Models of SARS-CoV2 Infection for COVID-19 Studies

为 COVID-19 研究建立 SARS-CoV2 感染的细胞模型

基本信息

批准号：
9924569
负责人：
Abraam M. Yakoub
金额：
$ 22.62万
依托单位：
UNIVERSITY OF NORTH DAKOTA
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-05-01 至 2021-08-04
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9924569
关键词：
2019-nCoV Acute Affect Animal Model Animals Anti-Inflammatory Agents Antigen-Antibody Complex Antiviral Agents Autophagocytosis Bacteria Basic Science Biological Assay C Type Lectin Receptors COVID-19 Cell model Cells Cessation of life Coronavirus Country Data Development Disease Disease model Equilibrium Event FDA approved Future Goals Growth Homeostasis Hospitalization Immune System Diseases Immune response Individual Infection Infection Control Infiltration Inflammation Inflammatory Response Innate Immune Response Integration Host Factors Interferon Type I Invaded Kinetics Klebsiella pneumoniae Knockout Mice Knowledge Lead Leukocytes Ligands Lower Respiratory Tract Infection Lung Mediating Modeling Molecular Monitor Mus Myeloid Cells Pathogenesis Pathologic Patients Pattern Pattern recognition receptor Phagocytes Phagocytosis Pharmaceutical Preparations Play Pneumonia Process Public Health Regulation Reporting Research Resolution Respiratory Failure Respiratory Tract Infections Role Sepsis Shapes Signal Transduction Symptoms TMPRSS2 gene Techniques Testing Therapeutic Intervention Tissues Tropism Tumor-infiltrating immune cells United States Vaccines Viral Viral Load result Virus Virus Diseases Writing antimicrobial cell type cofactor cytokine effective therapy immunoregulation mortality neutrophil novel pathogen prevent public health relevance receptor response septic therapeutic candidate therapeutic evaluation time use tissue tropism uptake virus tropism

项目摘要

Project Summary Coronavirus Disease of 2019 (COVID-19) is a US and global public health crisis. It has led to the deaths of, at the point of writing this application, over 476,000 patients and 10 million infected individuals worldwide. The US was the most affected country, with over 123,000 deaths thus far and over 2.4 M infections. COVID-19 is caused by a novel beta-coronavirus (CoV) known as Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV2), which was reported to cause severe pneumonia and lethal respiratory failure. There is no vaccine or FDA-approved drugs for COVID-19, and there is very little knowledge about this new virus at the basic science level. Thus, animal and cellular models are urgently needed to start to investigate the disease mechanism or test therapeutic interventions. Here, we propose to explore essential aspects of understanding COVID-19 viral infection: tissue tropism of the virus and antiviral innate immune responses of the host. Firstly, we will test viral tropism in various tissues relevant to reported COVID-19 symptoms and establish cellular models of the disease, by determining the expression of COVID-19 suggested entry receptor/cofactors, ACE2 and TMPRSS2, in various cell types and monitor the progress of infection over time using virus-specific assays and viral load quantification techniques. Secondly, we will test host cellular responses to SARS-CoV2 infection by determining the expression levels during infection, of proinflammatory cytokines and type-I interferons involved in antiviral defenses. We will also assess autophagy flux during infection, given that viruses gain growth advantage in cells by hijacking autophagy.

项目摘要 2019年冠状病毒病（COVID-19）是美国和全球公共卫生危机。在撰写本申请时，这导致了全球超过476,000名患者和1000万感染者的死亡。美国是受影响最大的国家，到目前为止，死亡人数超过123,000，感染了2.4 m。 Covid-19是由一种新型的β-核纳病毒（COV）引起的，称为严重的急性呼吸综合征冠状病毒2（SARS-COV2），据报道会导致严重的肺炎和致命的呼吸衰竭。 Covid-19没有疫苗或FDA批准的药物，并且在基础科学层面上对这种新病毒的了解很少。因此，迫切需要动物和细胞模型开始研究疾病机制或测试治疗干预措施。在这里，我们建议探索了解Covid-19的基本方面，即19号病毒感染：病毒的组织向量和宿主的抗病毒先天免疫反应。首先，我们将通过确定COVID-19的表达表明进入受体/辅助因子的表达，ACE2和TMPRSS2，在各种细胞类型中，在各种细胞类型中，使用病毒特异性分析和病毒载量量化技术在各种细胞类型中，在各种组织中测试与报道的COVID-19症状有关的各种组织中的病毒向手，并建立疾病的细胞模型。其次，我们将通过确定感染过程中的表达水平，促炎性细胞因子和I型干扰素参与抗病毒防御措施来测试宿主细胞对SARS-COV2感染的反应。鉴于病毒通过劫持自噬获得了细胞的生长优势，我们还将评估感染过程中自噬通量。