Intraspecies Transmission and Infectivity of Insectivore-Borne Hantaviruses

食虫动物传播的汉坦病毒的种内传播和感染性

• 批准号: 7903204
• 负责人: RICHARD YANAGIHARA
• 金额: $ 35.29万
• 依托单位: UNIVERSITY OF HAWAII AT MANOA
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-08 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7903204
• 关键词: Acute; Adult; Africa; American; Americas; Antibodies; Asia; Biological; Blood donor; Chronic Disease; Clinical; Clinical Distribution; Complex; Data; Detection; Diagnosis; Disease; Disease Outbreaks; Epidemiologist; Epidemiology; Etiology; Europe; Evolution; Fluorescence; Future; Genetic; Goals; Hantavirus; Hantavirus Pulmonary Syndrome; Health; Health Personnel; Hemorrhagic Fever with Renal Syndrome; Host-Parasite Relations; Human; Imagination; Infection; Island; Kidney Failure; Knowledge; Korea; Lead; Liquid substance; Lung diseases; Maintenance; Medical; Medicine; Molecular; Monoclonal Antibodies; Neutralization Tests; North America; Pathogenicity; Patients; Pattern; Phylogenetic Analysis; Physicians; Population; Population Dynamics; Probability; Pulmonary Heart Disease; Reagent; Recording of previous events; Research; Reverse Transcriptase Polymerase Chain Reaction; Rodent; Role; Serological; Serum; Shrews; Site; South Korea; Southwestern United States; Spatial Distribution; Syndrome; Techniques; Testing; Tissues; Viral Hemorrhagic Fevers; Virus; density; enzootic; epizootiology; genome sequencing; innovation; insight; next generation; prototype; public health relevance; transmission process; virus culture

DESCRIPTION (provided by applicant): A once-obscure group of rodent-borne viruses, known to cause hemorrhagic fever with renal syndrome (HFRS), gained immediate notoriety in the spring of 1993, when an outbreak of a rapidly progressive cardiopulmonary disease erupted in the Four Corners region of the southwestern United States. That a hantavirus, harbored by a neotomine rodent species identified as a reservoir host a decade earlier, would be responsible for this frequently fatal respiratory disease, now known as hantavirus pulmonary syndrome (HPS), was beyond the collective imagination of clinicians, epidemiologists and medical virologists. The realization that rodent-borne hantaviruses are capable of causing diseases as clinically disparate as HFRS and HPS raises the probability that hantaviruses recently detected in shrews would similarly cause a wide spectrum of disease. In-depth studies on the transmission dynamics and infectivity of Imjin virus (MJNV), recently isolated from the Ussuri shrew (Crocidura lasiura) in South Korea, may provide clues about its pathogenicity, as well as useful reagents to more rapidly diagnose future outbreaks of newly recognized diseases caused by emerging hantaviruses. The primary objectives of the proposed research are to determine the intraspecies transmission of MJNV and to ascertain its importance to human health and disease. Our central hypothesis is that MJNV is the prototype of a large clade of shrew-borne hantaviruses, which have co-evolved with their reservoir hosts and which are capable of causing infection, and possibly disease, in humans. Our experimental plan employs serological and molecular biological techniques for the detection and characterization of this new hantavirus and for the demonstration of human infection. Specific Aim 1. To determine the antigenic, genetic and phylogenetic relationships between MJNV and other hantaviruses. Specific Aim 2. To determine the host range, temporal occurrence and spatial distribution of MJNV infection. Specific Aim 3. To determine the infectivity and disease potential of MJNV in humans. The proposed research is innovative in that it challenges the long-held dogma that rodents are the sole reservoir hosts of hantaviruses. Newfound information about the evolutionary origin, host range and disease potential of MJNV will provide insights into the complex co-evolutionary history and host-parasite relationship of hantaviruses, which may lead ultimately to identifying the molecular determinants of hantavirus pathogenicity and tissue targeting. PUBLIC HEALTH RELEVANCE Carried by many species of rodents worldwide, hantaviruses are medically important viruses, which cause two distinct diseases in humans. One is a type of hemorrhagic fever with associated kidney failure occurring in Europe and Asia and the other is a rapidly progressive, frequently fatal respiratory disease occurring in the Americas. Recently, a new group of hantaviruses have been discovered in shrews. Because of their relatedness to disease-causing hantaviruses, the proposed research aims to determine if these newly identified hantaviruses cause infection and disease in humans. New knowledge about the shrew-borne hantaviruses will better prepare us to diagnose future outbreaks of hantavirus diseases.

描述（由申请人提供）：一组曾经发生的啮齿动物病毒组，已知会引起肾脏综合征（HFRS）的出血热，在1993年春季爆发，当时爆发了一种快速进行的进步心脏肺病爆发，在美国西南部美国西南部四个地点地区遭受了爆发。十年前被确定为储层宿主的新啮齿动物物种所备有的汉坦病毒将负责这种经常致命的呼吸道疾病，现在被称为汉塔病毒肺综合症（HPS），超出了临床医生，流行病学家和医学学家的集体想象。意识到，啮齿动物传播的汉坦病毒能够像HFRS和HP一样引起临床上的疾病，这会引起汉坦病毒最近在shreds中检测到的概率，同样会引起广泛的疾病。关于IMJIN病毒（MJNV）的传播动态和感染性的深入研究，最近与韩国的Ussuri Shrew（Crocidura Lasiura）分离出来，可能会提供有关其致病性的线索，以及其有用的试剂，以及有用的试剂，以更快地诊断出新认可的疾病爆发，这是由新认可的疾病爆发造成的，由Emerererseging Hantaviruses造成的新疾病。拟议研究的主要目标是确定MJNV的种内传播，并确定其对人类健康和疾病的重要性。我们的核心假设是MJNV是大型sh芽式汉塔病毒的原型，它们与储层宿主共同发展，能够在人类中引起感染或可能疾病。我们的实验计划采用血清学和分子生物学技术来检测和表征这种新的hantavirus和人类感染的演示。具体目的1。确定MJNV和其他汉坦病毒之间的抗原，遗传和系统发育关系。具体目标2。确定MJNV感染的宿主范围，时间发生和空间分布。具体目的3。确定人类MJNV的感染性和疾病潜力。拟议的研究具有创新性，因为它挑战了啮齿动物是唯一的汉坦病毒宿主的长期教条。有关MJNV的进化起源，宿主范围和疾病潜力的新发现的信息将提供有关汉坦病毒的复杂共同进化史和宿主关系的见解，这可能最终导致识别汉塔病毒致病性和组织靶标的分子决定因素。 全球许多啮齿动物携带的公共卫生相关性，汉坦病毒是医学上重要的病毒，在人类中引起两种不同的疾病。一种是一种出血热，在欧洲和亚洲发生了相关的肾衰竭，另一种是一种快速进行的，经常发生致命的呼吸道疾病。最近，在Shrews中发现了一群新的汉坦病毒。由于它们与引起疾病的汉坦病毒的相关性，拟议的研究旨在确定这些新鉴定的汉坦病毒是否引起人类感染和疾病。关于精明的汉坦病毒的新知识将更好地为我们做好准备，以诊断汉坦病毒疾病的未来爆发。