Fish Rhabdovirus--Model of RNA Virus Evolution

人类RNA病毒的特点是分离株之间的遗传变异大，突变速度快，对变化的环境有高效的适应能力。这项建议的目的和这项研究的长期目标是以鱼类弹状病毒作为模型系统，以更好地了解影响RNA病毒遗传变异和进化的机制。鱼病毒提供了一种独特的研究系统，因为鱼的宿主、水媒传播以及对鱼和活体鱼的温度要求较低，在样本大小和成本方面可能比其他脊椎动物更可行。该项目的具体目标是：1)通过对糖蛋白、基质和聚合酶基因内的可变区进行序列分析，表征温水鱼类横纹肌肉病毒、鲤鱼春季病毒血症(SVCV)整个范围(东欧)分离株的遗传多样性。结果将确定这种病毒的遗传多样性是否遵循先前对传染性造血坏死病毒(IHNV)和病毒性出血性败血症病毒(VHSV)的研究中发现的模式，这两种冷水鱼弹状病毒的遗传变异比哺乳动物弹状病毒小，还是SVCV具有更大的遗传多样性，可能是因为它是一种温水鱼类弹状病毒。2)研究温度(病毒复制率和碱基替换率)对SVCV遗传多样性和进化的影响。遗传多样性和进化将通过序列分析和适应度测量来衡量。从长远来看，将有可能比较SVCV和IHNV在细胞培养和体内系统中的进化，并确定温度对鱼类弹状病毒遗传变异和进化的影响。一次培养细胞，确定温度对鱼类弹状病毒遗传变异和进化的影响。一旦细胞培养和鱼类模型系统建立，就可以进行研究，检查影响鱼类弹状病毒进化的其他参数，如免疫选择的影响和毒力进化。这些人类疾病实验的意义将是揭示一类人类疾病实验的种群结构和进化，将揭示一类具有独特寄主和生态特征的病原体的种群结构和进化，这是以前没有详细研究过的。这些结果可以进一步阐明影响RNA病毒多样性、进化和毒力的机制。

Human RNA viruses are characterized by large genetic variation among isolates, rapid mutation rates and efficient adaptability to changing environments. The objective of this proposal and long-term goal of this research is to use fish rhabdoviruses as a model systems to better understand the mechanisms affecting the genetic variation and evolution of RNA viruses. Fish viruses offer a unique system to study because of the fish host., waterborne transmission, and lower temperature requirement for fish and in vivo fish may be more feasible than other vertebrates in terms of sample size and cost. The specific aims of this project are to: 1) Characterize the genetic diversity of a warm water fish rhabdovirus, spring viremia of carp (SVCV) isolates throughout its range (Eastern Europe) by conducting sequence analysis on variable regions within glycoprotein, matrix and polymerase genes. The results will determine if the genetic diversity of this virus follow the patterns found in previous studies involving infectious hematopoietic necrosis virus (IHNV) and viral hemorrhagic septicemia virus (VHSV), two cold water fish rhabdoviruses that have less genetic variation than mammalian rhabdoviruses or whether SVCV has grater genetic diversity perhaps because it is a warm water fish rhabdovirus. 2) Examine the effect of temperature (rate of virus replication and rate of base substitution) on the genetic diversity and evolution of SVCV. Genetic diversity and evolution will be measured by sequence analysis and measurements of fitness. Long-term it will be possible to compare the evolution of SVCV and IHNV in cell culture and in vivo systems and determine the influence of temperatures on genetic variation and evolution of fish rhabdoviruses. Once the cell and determine the influence of temperature on genetic variation and evolution of fish rhabdoviruses. Once the cell culture and fish model systems are established, studies examining other parameters affecting the evolution of fish rhabdoviruses can be done such as the impact of immune selection and the evolution of virulence. The significance of these experiments on human diseases will be to cast light on the population structure and evolution of a class of these experiments on human diseases will be to cast light on the population structure and evolution of a class of pathogen that have unique host and ecological characteristics that has not been investigated before in detail. The results can shed further light on the mechanisms effecting the diversity, evolution and virulence of RNA viruses.