Infection and prevalence of a new segmented flavivirus in the United States

美国新分段黄病毒的感染和流行

• 批准号: 10392327
• 负责人: Amit Kapoor
• 金额: $ 19.35万
• 依托单位: RESEARCH INST NATIONWIDE CHILDREN'S HOSP
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-13 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10392327
• 关键词: Africa; Animal Model; Animals; Biological; Biological Assay; Blood donor; Borrelia burgdorferi; Cell Culture Techniques; China; Chinese; Clinical Research; Code; Communicable Diseases; Complementary DNA; Coupled; Crimean Hemorrhagic Fever; Culicidae; Data; Deer Mouse; Development; Diagnostic Reagent; Disease; Domestic Animals; Europe; Evolution; Exposure to; Farm; Fever; Flavivirus; Future; Genetic; Genetic Variation; Genome; Genomic Segment; Goals; Hantavirus; Health; Hepatitis C virus; Human; Immunoprecipitation; Individual; Infection; Insecta; Knowledge; Kosovo; Letters; Livestock; Luciferases; Lyme Disease; Metagenomics; Molecular; Mus; Names; National Institute of Allergy and Infectious Disease; Nonstructural Protein; North America; Paramyxovirus; Pathogenesis; Patients; Pennsylvania; Peromyscus; Phylogenetic Analysis; Poly A; Polymerase; Polyproteins; Powassan virus; Prevalence; Prevention; Proteins; Province; RNA; RNA Viruses; Reagent; Recording of previous events; Replicon; Reporting; Reverse Transcriptase Polymerase Chain Reaction; Rodent; Route; Sampling; Sensitivity and Specificity; Serology; Serology test; Serum; Source; South America; Structural Protein; System; Testing; Ticks; United States; United States National Institutes of Health; Variant; Vertebrates; Viral; Virus; Virus Diseases; Walking; Yellow Fever; Zoonoses; animal coronavirus; base; deep sequencing; diagnostic assay; genome sequencing; helicase; innovation; prevent; public health relevance; reagent testing; research study; reverse genetics; tick bite; tick transmission; virome; virus development

Summary/abstract Segmented RNA viruses that share phylogenetic relatedness with the prototypic Flaviviruses in their helicase (NS3) and polymerase (NS5) proteins were recently identified from ticks, mosquitoes, and vertebrates, including humans suffering with febrile illness. The first Flavi-like segmented viruses (FLSV) were isolated from ticks and animals in the Jingmen province of China and were thus named Jingmen Tick Virus. Subsequently, highly diverse FLSV variants were found in Africa, Europe and South America. However, no evidence of FLSV infection has been reported in North America, including the United States. Moreover, several recent studies that used metagenomics-based identification of the virome in ticks failed to identify FLSV infection. We were characterizing the virome of free-ranging mice of the genus Peromyscus, the most common wild mouse species of the North America, when we identified a highly diverse FLSV in several deer mice from woodlands in Pennsylvania (FLSV- PN). We acquired partial sequences of all five segments of the FLSV-PN genome and developed serological assays using Luciferase immunoprecipitation systems. Our serological data suggest that FLSV-PN or its related variants have a wide host range and infect several economically important farm and domestic animals. Most importantly, we found strong evidence of FLSV-PN infection in humans with a history of tick-bites and Lyme disease. The long-term goal of our exploratory/developmental proposal is to define the pathogenesis and health relevance of FLSV-PN infection. Development of molecular reagents for this new virus will allow us to test our hypotheses that several genetically diverse FLSV variants are circulating in the United States, and these viruses are predominantly transmitted by ticks to humans and animals. Specific aim-1 is to acquire the complete genomes of several diverse FLSV variants. Our preliminary data suggest that FLSV-PN genome is comprised of five RNA segments that are polyadenylated at the 3’ end. Complete genome sequencing of FLSV-PN is necessary for the development of sensitive and specific diagnostic assays to study infection prevalence and disease associations. Specific aim-2 is to determine the infection prevalence of FLSV in humans, domesticated animals and ticks. These studies will be aided by samples and data available from clinical research studies of Lyme disease at NIAID, NIH (letter of support attached). The proposed aims represent crucial steps toward detailed molecular and biological characterization of FLSV-PN, including the development of a reverse genetics system, replicon systems, cell culture and animal models. Although the health relevance of FLSV infections is currently not known, the proposed studies will inform this knowledge as well as develop the reagents for preventing the spread of this new virus and associated diseases, if necessary.

摘要/摘要 分段 RNA 病毒的解旋酶与原型黄病毒具有系统发育相关性 最近从蜱虫、蚊子和脊椎动物中发现了 (NS3) 和聚合酶 (NS5) 蛋白，包括 患有热病的人。第一个类 Flavi 分段病毒（FLSV）是从蜱中分离出来的 荆门蜱病毒源自中国荆门省的动物，因此被命名为荆门蜱病毒。随后，高度多样化 FLSV 变种在非洲、欧洲和南美洲发现。然而，目前尚无 FLSV 感染证据 包括美国在内的北美地区均有报道。此外，最近的几项研究使用 基于宏基因组学的蜱病毒组鉴定未能识别 FLSV 感染。我们正在描述 北白鼠属自由放养小鼠的病毒组，白鼠属是北方最常见的野生小鼠物种 美国，当我们在宾夕法尼亚州林地的几只鹿鼠中发现了高度多样化的 FLSV（FLSV- PN）。我们获得了 FLSV-PN 基因组所有五个片段的部分序列，并开发了血清学 使用荧光素酶免疫沉淀系统进行测定。我们的血清学数据表明 FLSV-PN 或其相关 变种具有广泛的宿主范围并感染几种具有重要经济意义的农场和家畜。最多 重要的是，我们在有蜱虫叮咬和莱姆病史的人类中发现了 FLSV-PN 感染的有力证据 疾病。我们探索/开发提案的长期目标是确定发病机制和健康 FLSV-PN 感染的相关性。针对这种新病毒的分子试剂的开发将使我们能够测试我们的 假设几种基因多样的 FLSV 变种正在美国传播，并且这些病毒 主要通过蜱传播给人类和动物。具体目标1是获得完整的 几种不同 FLSV 变种的基因组。我们的初步数据表明 FLSV-PN 基因组包含 5 个 RNA 片段在 3' 端被聚腺苷酸化。 FLSV-PN 的完整基因组测序是 开发敏感且特异的诊断方法以研究感染流行率和 疾病协会。具体目标 2 是确定 FLSV 在人类、驯化动物中的感染率 动物和蜱虫。这些研究将得到来自临床研究的样本和数据的帮助 NIAID、NIH 的莱姆病（附支持信）。拟议的目标是实现这一目标的关键步骤 FLSV-PN 的详细分子和生物学特征，包括反向遗传学的开发 系统、复制子系统、细胞培养和动物模型。尽管 FLSV 感染与健康的相关性 目前尚不清楚，拟议的研究将提供这些知识并开发试剂 如有必要，防止这种新病毒和相关疾病的传播。

项目成果

Development and Validation of Indirect Enzyme-Linked Immunosorbent Assays for Detecting Antibodies to SARS-CoV-2 in Cattle, Swine, and Chicken.

间接酶联免疫吸附剂的开发和验证，用于检测牛，猪和鸡肉中SARS-COV-2的抗体。

• DOI: 10.3390/v14071358
• 发表时间: 2022-06-22
• 期刊: Viruses

SARS-CoV-2 Omicron (B.1.1.529) Infection of Wild White-Tailed Deer in New York City.

• DOI: 10.3390/v14122770
• 发表时间: 2022-12-12
• 期刊: Viruses
• 作者: Vandegrift KJ;Yon M;Surendran Nair M;Gontu A;Ramasamy S;Amirthalingam S;Neerukonda S;Nissly RH;Chothe SK;Jakka P;LaBella L;Levine N;Rodriguez S;Chen C;Sheersh Boorla V;Stuber T;Boulanger JR;Kotschwar N;Aucoin SG;Simon R;Toal KL;Olsen RJ;Davis JJ;Bold D;Gaudreault NN;Dinali Perera K;Kim Y;Chang KO;Maranas CD;Richt JA;Musser JM;Hudson PJ;Kapur V;Kuchipudi SV
• 通讯作者: Kuchipudi SV

Transmission history of SARS-CoV-2 in humans and white-tailed deer.

人类和白尾鹿的SARS-COV-2传播历史。

• DOI: 10.1038/s41598-022-16071-z
• 发表时间: 2022-07-15
• 期刊: SCIENTIFIC REPORTS
• 影响因子: 4.6
• 作者: Willgert, Katriina;Didelot, Xavier;Surendran-Nair, Meera;Kuchipudi, Suresh, V;Ruden, Rachel M.;Yon, Michele;Nissly, Ruth H.;Vandegrift, Kurt J.;Nelli, Rahul K.;Li, Lingling;Jayarao, Bhushan M.;Levine, Nicole;Olsen, Randall J.;Davis, James J.;Musser, James M.;Hudson, Peter J.;Kapur, Vivek;Conlan, Andrew J. K.
• 通讯作者: Conlan, Andrew J. K.