Characterization of cougar lentiviruses

美洲狮慢病毒的表征

基本信息

批准号：
6654290
负责人：
Mary L. Poss
金额：
$ 14万
依托单位：
UNIVERSITY OF MONTANA
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-06-01 至 2006-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6654290
关键词：
animal ecology biochemical evolution disease outbreaks emerging infectious disease environmental adaptation feline immunodeficiency virus functional /structural genomics health science research potential host organism interaction nucleic acid sequence pathologic process regulatory gene role model tissue /cell culture virus DNA virus genetics virus infection mechanism virus replication

项目摘要

DESCRIPTION (provided by applicant): In the last 2 decades, both humans and domestic cats have become new hosts for lentivirus. Infection results in progressive immunodeficiency and death in both hosts. In contrast to the disease induced by a lentivirus in a new host species, infection of many feline and primate species is apparently apathogenic, presumably because of a long history of co-adaptation between virus and host. There has been very little research on virus and host factors that lead to apathogenic outcomes of animals naturally infected with lentiviruses. Knowledge of mechanisms that lead to apathogenic, endemic lentivirus infections will provide an essential framework to investigate the pathogenesis and evolution of epidemic lentivirus infections. In order to develop an understanding of endemic feline lentiviruses, we have investigated the epidemiology and molecular evolution of a species-specific feline lentivirus (FIVFco) in wild cougars (Fells concolor) in the western United States. The seroprevalence of FIVFco exceeds 50% in most populations, virus populations evolve at 1.5%/decade, and there is selection against change of viral structural proteins. To further advance this important model, we will initiate studies to discern potential viral mechanisms for a pathogenic infection of FIVFco. We reason that because accessory genes control virus replication and virus-host cell interactions, the arrangement, expression patterns, or function of lentiviral regulatory genes may differ between FIV and FIVFco. In this proposal we will test the hypothesis that the genomic structure of pathogenic FIV and a pathogenic FIVFco will differ in the organization of accessory genes. To address this hypothesis, we will isolate FIVFco genomes that are representative of diverse lineages that we have identified in infected western US cougars, sequence the entire genome, determine genomic organization of FIVfco and compare the genomes of FIVfco and FIV The Specific Aims of the proposal are: Specific Aim 1. To isolate cougar lentiviruses from naturally infected animals; Specific Aim 2. To determine the genomic organization of FIVfco from culture supernatants and tissue DNA; Specific Aim 3. To mentor students in infectious disease research.

描述（申请人提供）：近20年来，人类和家猫都成为慢病毒的新宿主。感染会导致宿主进行性免疫缺陷和死亡。与慢病毒在新宿主物种中诱发的疾病相比，许多猫科动物和灵长类动物的感染显然是非致病性的，这可能是因为病毒与宿主之间长期的共同适应历史。对于导致自然感染慢病毒的动物出现非致病性结果的病毒和宿主因素的研究很少。了解导致非致病性、地方性慢病毒感染的机制将为研究流行性慢病毒感染的发病机制和演变提供重要框架。为了加深对地方性猫科慢病毒的了解，我们研究了美国西部野生美洲狮（Fells concolor）中物种特异性猫科慢病毒（FIVFco）的流行病学和分子进化。在大多数人群中，FIVFco 的血清流行率超过 50%，病毒种群以每十年 1.5% 的速度进化，并且存在针对病毒结构蛋白变化的选择。为了进一步推进这一重要模型，我们将启动研究来辨别 FIVFco 致病性感染的潜在病毒机制。我们推断，由于辅助基因控制病毒复制和病毒与宿主细胞的相互作用，慢病毒调节基因的排列、表达模式或功能在 FIV 和 FIVFco 之间可能有所不同。在本提案中，我们将检验以下假设：致病性 FIV 和致病性 FIVFco 的基因组结构在辅助基因的组织上有所不同。为了解决这一假设，我们将分离代表我们在受感染的美国西部美洲狮中鉴定出的不同谱系的 FIVFco 基因组，对整个基因组进行测序，确定 FIVfco 的基因组组织并比较 FIVfco 和 FIV 的基因组。该提案的具体目标具体目的 1. 从自然感染的动物中分离美洲狮慢病毒；具体目标 2. 从培养物上清液和组织 DNA 中确定 FIVfco 的基因组结构；具体目标 3. 指导学生进行传染病研究。