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

基本信息

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
项目类别：
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

项目摘要

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，包括第一个类黄节段病毒（FLSV）是从蜱虫和患有发热性疾病的人类中分离出来的。荆门蜱病毒是中国荆门省的一种动物，因此被高度命名为荆门蜱病毒。非洲、欧洲和南美洲发现了 FLSV 变种，但尚无 FLSV 感染的证据。包括美国在内的北美地区也有报道称，最近的一些研究使用了这种方法。基于宏基因组学的蜱病毒组鉴定未能识别 FLSV 感染。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- 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数据。使用荧光素酶免疫沉淀系统进行的检测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多种经济上重要的农场和家畜。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 感染的有力证据我们探索/开发提案的长期目标是确定发病机制和健康状况。开发针对这种新病毒的分子试剂将使我们能够测试我们的病毒。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是获得完整的病毒。我们的初步数据表明，FLSV-PN 基因组包含多种不同的 FLSV 变体。 FLSV-PN 的 5 个 3' 端多聚腺苷酸化的 RNA 片段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具体目标 2 是确定人类驯化的 FLSV 感染流行率。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）。 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 感染的健康相关性是有限的。目前尚不清楚，拟议的研究将提供这一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

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

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
影响因子：
0
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.

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.

Detection of SARS-CoV-2 Omicron variant (B.1.1.529) infection of white-tailed deer.