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， 包括美国在内最近在南美洲和墨西哥爆发的疫情 强调了VEE出现的持续威胁。VEE病毒集中体现了 RNA病毒突变和改变其宿主范围和疾病的能力 模式，并代表理想的模型系统的研究RNA-和 虫媒病毒病的出现。VEE研究60年的开创性问题 一直是导致人类和马的主要疾病的菌株的来源 爆发我们的流行病学和遗传学研究表明， LkB和IC亚型动物流行病毒是从地方流行的ID亚型病毒进化而来的 在委内瑞拉和哥伦比亚持续流通。反向遗传学研究 表明少量的突变可以产生亚型IC菌株， ID祖细胞，并暗示带正电荷的E2包膜糖蛋白氨基 1992-93年爆发的酸变化。实地研究发现， 祖先地方病传播周期的关键宿主，以及 卫星图像已经被开发用于预测广泛的地理范围 地方性病毒传播的地点流行病学和遗传学 数据还表明，动物流行病病毒在停止 爆发，提高了VEE出现的可能性，而不需要 突变所有这些突发事件都对公共卫生 影响 使用感染性cDNA克隆技术的独特组合， 感染，和实地研究，拟议的研究将回答关键， 关于VEE出现的剩余问题：1）在E2中进行类似的更改 糖蛋白解释了先前LkB和IC动物流行病毒的出现; 2） 地方流行的VEE病毒的其他基因型是否能够突变成为 动物流行病，还是地方流行病祖先的遗传骨干限制了它的 能变成马的毒力吗3)动物流行病病毒是如何通过 在森林生境中的地方病菌株突变，转移到 在生态条件允许爆发的地方？还有，4） 动物流行性菌株在停止感染后持续存在， 爆发？ 我们的研究结果将促进对VEE出现机制的理解， 预测拉丁美洲和佛罗里达可能出现的地点。这 信息对于确定预防和控制资源的目标是非常宝贵的， 特别是为了在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.