Intraspecies Transmission and Infectivity of Insectivore-Borne Hantaviruses

描述（由申请人提供）：1993年春天，当美国西南部的四角地区爆发一种快速进展的心肺疾病时，一组曾经不为人知的啮齿动物传播病毒（已知可引起肾综合征出血热（HFRS））立即声名狼借。十年前被确定为储库宿主的一种啮齿类新动物物种所携带的汉他病毒，将负责这种经常致命的呼吸道疾病，现在称为汉他病毒肺综合征（HPS），超出了临床医生，流行病学家和医学病毒学家的集体想象。啮齿动物传播的汉他病毒能够引起临床上完全不同的疾病，如HFRS和HPS，这一认识提高了最近在鼩 鼱中检测到的汉他病毒同样会引起广泛疾病的可能性。对最近从韩国乌苏里鼩（Crocidura lasiura）中分离出的临津江病毒（MJNV）的传播动力学和感染性进行深入研究，可能会提供有关其致病性的线索，以及有用的试剂，以更快地诊断未来由新兴汉坦病毒引起的新认识疾病的暴发。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是一个大的分支的鼩传汉他病毒，共同进化与他们的水库主机和能够引起感染，并可能在人类疾病的原型。我们的实验计划采用血清学和分子生物学技术检测和表征这种新的汉坦病毒，并证明人类感染。具体目标1。目的探讨MJNV与其他汉坦病毒的抗原性、遗传学和系统发育关系。具体目标2。目的：明确MJNV感染的寄主范围、发生时间和空间分布。具体目标3。确定MJNV在人类中的感染性和致病潜力。这项研究是创新的，因为它挑战了长期以来的教条，即啮齿动物是汉坦病毒的唯一储存宿主。有关MJNV的进化起源、宿主范围和疾病潜力的新发现将为汉坦病毒复杂的共同进化历史和宿主-寄生虫关系提供深入了解，这可能最终导致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，由世界各地的许多啮齿动物携带，在人类中引起两种不同的疾病。一种是在欧洲和亚洲发生的伴有肾衰竭的出血热，另一种是在美洲发生的快速进行性、经常致命的呼吸道疾病。最近，一组新的汉坦病毒已被发现的鼩。由于它们与致病的汉他病毒相关，拟议的研究旨在确定这些新发现的汉他病毒是否会引起人类感染和疾病。有关鼩 鼱传播的汉他病毒的新知识将使我们更好地诊断未来的汉他病毒疾病暴发。

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.