ECOLOGY AND GENETICS OF VENEZUELAN EQUINE ENCEPHALITIS

描述：委内瑞拉马脑炎(VEE)是一种新兴的虫媒病毒 疾病以及整个美洲的公共和兽医健康威胁， 包括美国在内。南美和墨西哥最近的疫情 强调VEE出现的持续威胁。VEE病毒集中体现了 RNA病毒变异和改变寄主范围和疾病的能力 模式，代表了研究RNA-和的理想模型系统 虫媒病毒病出现。VEE研究60年的开创性问题 一直是人类和马的主要致病菌株的来源 疫情爆发。我们的流行病学和遗传学研究表明， LKB亚型和IC亚型流行性感冒病毒由地方性、亚型ID病毒进化而来 在委内瑞拉和哥伦比亚持续流传。反向遗传学研究 表明少量突变可以产生亚型IC毒株 ID祖细胞，并涉及带正电的E2包膜糖蛋白氨基酸 1992-93年暴发时出现的酸变。实地调查发现 先祖地方病传播周期的关键宿主，以及 卫星图像已被开发用于在广泛的地理范围内进行预测 地方性病毒传播的地方。流行病学和遗传学 数据还表明，家畜流行病病毒在停止传播后持续存在。 暴发，增加了VEE出现而不需要 突变。所有这些突发事件都有深刻的公共卫生问题。 这意味着什么。 利用独一无二的感染性cDNA克隆技术，实验性 感染和实地研究，拟议的研究将回答关键的， 关于VEE出现的剩余问题：1)在E2中是否有类似的变化 糖蛋白解释以前的LKB和IC流行性病毒的出现；2) 地方性VEE病毒的其他基因类型是否能够突变为 是流行性的，还是地方性祖先的遗传主干限制了它的 有能力成为马的毒力吗？3)流行性感冒病毒是如何通过 地方性生境中地方性菌株的突变，运输到不同的地点 在生态条件允许引发疫情的地方？以及，4)做 流行性出血热病毒株在停止流行后持续循环 暴发？ 我们的结果将促进对VEE出现机制的理解，并将 预测拉丁美洲和佛罗里达州可能出现疫情的地点。这 信息在针对预防和控制资源方面将是无价的， 尤其是在有限的发展中国家获得最大利益 资源。

DESCRIPTION: Venezuelan equine encephalitis (VEE) is an emerging arboviral disease and a public and veterinary health threat throughout the Americas, including the United States. Recent outbreaks in South America and Mexico underscore the continued threat of VEE emergence. VEE virus epitomizes the ability of RNA viruses to mutate and alter their host range and disease patterns, and represents ideal model systems for the study of RNA- and arboviral disease emergence. The seminal question in 60 years of VEE research has been the source of the strains responsible for major human and equine outbreaks. Our epidemiological and genetic studies indicate that epizootic, subtype LkB and IC epizootic viruses evolve from enzootic, subtype ID viruses that circulate continuously in Venezuela and Colombia. Reverse genetic studies indicate that small numbers of mutations can generate subtype IC strains from ID progenitors, and implicate positively charged E2 envelope glycoprotein amino acid changes in emergence of a 1992-93 outbreak. Field studies have identified the critical hosts of the progenitor enzootic transmission cycles, and satellite imagery has been developed to predict over a broad geographical range the locations where enzootic viruses circulate. Epidemiological and genetic data also suggest that epizootic viruses persist following the cessation of outbreaks, raising the possibility of VEE emergence without the need for mutation. All of these emergence scenarios have profound public health implications. Using a unique combination of infectious cDNA clone technology, experimental infections, and field studies, the proposed research will answer critical, remaining questions regarding VEE emergence: 1) do similar changes in the E2 glycoprotein explain the emergence of previous LkB and IC epizootic viruses; 2) are other genotypes of enzootic VEE viruses capable of mutating to become epizootic, or does the genetic backbone of the enzootic progenitor limit its ability to become equine virulent? 3) How are epizootic viruses, generated via mutation of enzootic strains in sylvatic habitats, transported to locations where ecological conditions permit the initiation of outbreaks? And, 4) do epizootic strains persist in continuous cycles following the cessation of outbreaks? Our results will advance understanding of VEE emergence mechanisms, and will predict locations of potential emergence in Latin America and Florida. This information will be invaluable in targeting prevention and control resources, especially for obtaining maximum benefit in developing countries with limited resources.