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: 7668615
• 负责人: RICHARD YANAGIHARA
• 金额: $ 42.49万
• 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/7668615
• 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）：一组曾经不为人知的啮齿动物传播病毒，已知会引起肾综合征出血热 (HFRS)，1993 年春天，美国西南部四角地区爆发了一种快速进展的心肺疾病，该病毒立即声名狼藉。十年前被确定为储存宿主的新托明啮齿类动物携带的汉坦病毒会导致这种常见的致命呼吸道疾病，现在被称为汉坦病毒肺综合征（HPS），这超出了临床医生、流行病学家和医学病毒学家的集体想象。认识到啮齿动物传播的汉坦病毒能够引起与 HFRS 和 HPS 等临床上不同的疾病，这增加了最近在鼩鼱中检测到的汉坦病毒同样会引起广泛疾病的可能性。最近从韩国乌苏里鼩鼱 (Crocidura lasiura) 中分离出的 Imjin 病毒 (MJNV) 的传播动力学和感染性的深入研究可能会提供有关其致病性的线索，并提供有用的试剂来更快速地诊断由新兴汉坦病毒引起的新发现疾病的未来爆发。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。我们的中心假设是，MJNV 是鼩鼱传播的汉坦病毒大分支的原型，这些病毒与其储存宿主共同进化，能够引起人类感染，甚至可能导致疾病。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型汉坦病毒并演示人类感染。具体目标 1. 确定 MJNV 与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。具体目标 3. 确定 MJNV 在人类中的传染性和疾病潜力。这项研究的创新之处在于，它挑战了长期以来认为啮齿类动物是汉坦病毒唯一储存宿主的教条。关于 MJNV 的进化起源、宿主范围和疾病潜力的新发现信息将为了解汉坦病毒复杂的共同进化历史和宿主-寄生虫关系提供见解，这可能最终确定汉坦病毒致病性和组织靶向的分子决定因素。 公共卫生相关性 汉坦病毒是医学上重要的病毒，由全世界多种啮齿类动物携带，可引起人类两种不同的疾病。一种是发生在欧洲和亚洲的一种与肾衰竭相关的出血热，另一种是发生在美洲的一种快速进展、常常致命的呼吸道疾病。最近，在鼩鼱身上发现了一组新的汉坦病毒。由于它们与致病的汉坦病毒相关，拟议的研究旨在确定这些新发现的汉坦病毒是否会引起人类感染和疾病。关于鼩鼱传播的汉坦病毒的新知识将使我们更好地诊断汉坦病毒疾病的未来爆发。