Suppression of viral RNA recombination by host genes

摘要：Peter D. Nagy，提案号：0517218宿主基因抑制病毒RNA重组。新RNA病毒的出现通常是由于RNA重组，这是一个将不连续的RNA片段连接在一起的过程。重组产生的基因、序列基序或调控RNA序列的新组合可能导致RNA病毒的感染性发生巨大变化。这反过来又有助于病毒跨越物种，克服自然抗性机制，并使疫苗和其他抗病毒方法无效。为了进一步了解宿主在病毒RNA重组中的作用，PI最近开发了基于酵母的模式植物病毒黄瓜坏死瘤病毒（CNV）的复制和重组系统。这种方法鉴定出了5种抑制病毒RNA重组的宿主基因。为了描述已鉴定的宿主因子在RNA重组中的作用，PI将使用先进的酵母遗传学工具与生化方法相结合。本研究的潜在影响：本文描述的研究将有助于更好地理解宿主基因对RNA重组的影响以及宿主在病毒进化中的作用。由于宿主基因在病毒RNA重组中的作用目前尚不清楚，因此这项工作可能会极大地改变我们对宿主在病毒RNA重组中的作用的看法。拟议工作的更广泛影响：这笔拨款将允许在PI的实验室培训高中和本科生。这项研究将促进跨学科（植物病理学、生物化学、遗传学）的学习。这项研究有望在病毒重组/进化和新病毒出现领域取得突破性成果，从而造福社会。

Abstract: Peter D. Nagy, Proposal number: 0517218Suppression of viral RNA recombination by host genes. Emergence of new RNA viruses is frequently due to RNA recombination, a process that joins noncontiguous RNA segments together. Novel combinations of genes, sequence motifs or regulatory RNA sequences resulting from recombination may cause dramatic changes in the infectious properties of RNA viruses. This, in turn, helps viruses to jump species, to overcome natural resistance mechanisms and renders vaccines and other antiviral methods ineffective. In order to advance our understanding of the role of the host in viral RNA recombination, the PI has recently developed yeast-based replication and recombination systems for a model plant virus, Cucumber necrosis tombusvirus (CNV). This approach led to the identification of five host genes suppressing viral RNA recombination. To characterize the roles of the identified host factors in RNA recombination, the PI will use the advanced genetics tools available for yeast in combination with biochemical approaches. Potential impact of the proposed work: The research described here will lead to better understanding of the effect of host genes on RNA recombination and the role of the host in virus evolution. Because the role of host genes in viral RNA recombination is currently unknown, the proposed work may dramatically change our view of the role of the host in viral RNA recombination. Broader impacts of the proposed work: This grant will allow training of high school and undergraduate students in the PI's laboratory. This research will promote interdisciplinary (plant pathology, biochemistry, genetics) learning. The research holds promise of benefiting society by leading to groundbreaking results in the area of virus recombination/evolution and the emergence of new viruses.