Interactions of Emerging Bunyaviruses with Host Cells

新兴布尼亚病毒与宿主细胞的相互作用

• 批准号: 7670061
• 负责人: Robert W. Doms
• 金额: $ 33万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-03 至 2014-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7670061
• 关键词: Abortion Rates; Acute; Africa; Andes Virus; Antibodies; Antiviral Agents; Biological Assay; Bunyaviridae; Case Fatality Rates; Categories; Cell Communication; Cells; Centers for Disease Control and Prevention (U.S.); Cherry - dietary; Codon Nucleotides; Collaborations; Computer Retrieval of Information on Scientific Projects Database; Culicidae; Databases; Development; Disease Outbreaks; Domestic Animals; Economics; Emerging Communicable Diseases; Family; Fever; Funding; Genes; Genetic; Genome; Genus Phlebovirus; Goals; Grant; Hantavirus; Hantavirus Pulmonary Syndrome; Hemorrhagic Fever with Renal Syndrome; Hepatic; Human; Infection; Insecta; Kenya; Libraries; Mammalian Cell; Nairovirus; Orthobunyavirus; Pathway interactions; Pennsylvania; Puumala virus; RNA Interference; Reagent; Request for Applications; Research Personnel; Retinal; Rift Valley fever virus; Rodent; Screening procedure; Series; Sin Nombre virus; Symptoms; Testing; Therapeutic; Therapeutic Intervention; United States Department of Agriculture; Universities; Vaccines; Viral; Virus; Virus Replication; Work; base; biodefense; cell type; cellular targeting; high throughput technology; member; pathogen; small molecule; small molecule libraries; tool

The family Bunyaviridae consists of over 300 viruses with members of four Bunyaviridae genera (Hantavirus, Orthobunyavirus, Phlebovirus and Nairovirus) infecting humans. A number of the Hantaviruses and Rift Valley Fever virus (RVFV, a Phlebovirus) are Category A agents with RVFV being of particular concern. RVFV, which is spread by infected mosquitoes, was first described in Kenya in 1931 and has since been documented throughout much of Africa and the Arabian peninsula. RVFV causes acute fevers and, sometimes, retinal or hepatic complications with hemorrhagic symptoms. A recent outbreak in Kenya had a case-fatality rate of greater than 20% for those with severe illness. In addition, RVFV causes catastrophic abortion rates in domesticated animals, and thus can causes significant economic losses. As a result, it is categorized as an overlap select agent by both the CDC and the US Department of Agriculture. Also of concern are a number of Hantaviruses that cause hantavirus pulmonary syndrome (HPS) and/or hemorrhagic fever with renal syndrome (HFRS) in humans. Included among these rodent-borne viruses are Sin Nombre virus, Andes virus, and Puumala virus. RVFV and hantaviruses are under-studied pathogens for which there are no approved vaccines or therapeutics. With support from the MARCE beginning in 2005, we launched an effort to study RVFV and, more recently, several hantaviruses. Working with colleagues at USAMRIID, the CDC and at Penn, we have developed a series of genetic tools and functional assays that are being used in high throughput, whole genome RNAi and chemical library screens to identify host cell molecules and pathways needed for the replication and dissemination of these viruses. Significant progress with RVFV has already been made. By studying several bunyaviruses, we hope to identify cellular pathways that are common to this virus family, as well as to identify cellular molecules that are uniquely important to specific viral agents. The overall goal of our project is to identify host cell targets for therapeutic intervention. Specifically, we propose to: 1. Complete our whole genome RNAi and chemical library screens with RVFV, validate hits and determine mechanism of action. 2. Develop the genetic tools, assays and reagents needed to perform whole genome RNAi and chemical library screens for Sin Nombre virus. 3. Determine breadth of action by testing against Andes and Puumala.

Bunyaviridae家族由300多个病毒组成，有四个Bunyaviridae属的成员（汉塔病毒， 骨性病毒，静脉病毒和奈罗维病毒）感染了人类。许多汉坦病毒和裂谷 山谷发烧病毒（RVFV，A phlebovirus）是A类药物，其RVFV特别关注。 由感染蚊子传播的RVFV于1931年首次在肯尼亚进行了描述，此后一直是 记录在非洲和阿拉伯半岛的大部分地区。 RVFV会引起急性发烧，并 有时，具有出血症状的视网膜或肝并发症。最近在肯尼亚的一次爆发有一个 患有严重疾病的人的病例竞争率大于20％。此外，RVFV会导致灾难性 驯养动物的堕胎率，因此可能造成巨大的经济损失。结果，是 由疾病预防控制中心和美国农业部归类为重叠选择代理。也是 关注的是许多引起汉坦病毒肺综合征（HPS）和/或的汉坦病毒 人类的肾脏综合征（HFRS）出血热。其中包括这些啮齿动物传播病毒 Sin nombre病毒，安第斯山脉病毒和puumala病毒。 RVFV和汉坦病毒是研究不足的病原体 没有批准的疫苗或治疗剂。在2005年开始的马尔斯的支持下， 我们发起了研究RVFV的努力，最近几个hantaviruess。与同事合作 Usamriid，CDC和Penn，我们开发了一系列的遗传工具和功能测定法 在高吞吐量，整个基因组RNAi和化学库筛选中用于识别宿主细胞 这些病毒复制和传播所需的分子和途径。取得重大进展 已经制作了RVFV。通过研究几个Bunyavirus，我们希望识别细胞途径 该病毒家族常见的，以及鉴定细胞分子，这些分子对 特定的病毒剂。我们项目的总体目标是确定治疗干预的宿主细胞目标。 具体来说，我们建议： 1。用RVFV完成我们的整个基因组RNAI和化学库筛选，验证命中和 确定作用机理。 2。开发执行整个基因组RNAI所需的遗传工具，测定和试剂 化学图书馆的罪恶nombre病毒。 3。通过对安第斯山脉和普马拉的测试来确定作用广度。