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Effect of tissue tropism on RNA viral evolutionary rates: three family-level anal

组织向性对 RNA 病毒进化速率的影响：三个科水平的分析

基本信息

批准号：
8339436
负责人：
SIOBAIN M DUFFY
金额：
$ 7.75万
依托单位：
RUTGERS, THE STATE UNIV OF N.J.
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-30 至 2013-08-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): RNA viruses mutate and evolve more quickly than all other human pathogens. However, RNA viruses do not all evolve at the same fast rate. It is important to distinguish the faster evolving RNA viruses because they are more likely to create drug-resistant variants or evade vaccine-induced immune responses. Whole families of RNA viruses are known to be more evolvable than others, but we know very little about what causes individual viruses to evolve more rapidly than closely related viruses in the same family. We will test whether tissue tropism could be one of the factors affecting evolutionary rates. Specifically, we are testing if genes within enteric viruses, those that infect the gastro-intestinal tract, evolve more quickly than related viruses that infect other tissues in the same hosts. Long-term nucleotide substitution rates will be calculated from members of three important RNA virus families that have large numbers of sequences in GenBank: Caliciviridae, which include the leading cause of foodborne illness in this country, Picornaviridae, which include poliovirus, and Reoviridae, which include rotavirus, the most common cause of infant diarrhea worldwide. We will contrast the rates of evolution of the same gene in primarily enteric and primarily non-enteric viruses, which will allow us an apples-to-apples comparison between viruses. The BEAST software we use takes a Bayesian phylogenetic coalescent approach to calculating evolutionary rates. The accuracy of such estimates changes over different timescales, and the time to the coalescent of some of our analyses varies over an order of magnitude (i.e., some data coalesce in 70 years, others in 700 years). Since many of the enteric virus data sets coalesce more quickly than the non-enteric virus data sets, additional controls will be conducted to ensure our results are not biased by coalescent time. Our work has the potential to open up avenues of research into whether enteric tissue tropism mechanistically leads to faster rates of RNA viral evolution, and to highlight weaknesses in a widely used software program.

描述（由申请人提供）： RNA 病毒的突变和进化速度比所有其他人类病原体都快。然而，RNA 病毒的进化速度并不相同。区分进化速度较快的 RNA 病毒非常重要，因为它们更有可能产生耐药变体或逃避疫苗诱导的免疫反应。众所周知，RNA 病毒的整个家族比其他病毒更容易进化，但我们对是什么导致单个病毒比同一家族中密切相关的病毒进化得更快的原因知之甚少。我们将测试组织向性是否可能是影响进化速率的因素之一。具体来说，我们正在测试感染胃肠道的肠道病毒中的基因是否比感染同一宿主其他组织的相关病毒进化得更快。长期核苷酸替代率将根据 GenBank 中拥有大量序列的三个重要 RNA 病毒家族的成员进行计算：杯状病毒科（包括该国食源性疾病的主要原因）、小核糖核酸病毒科（包括脊髓灰质炎病毒）和呼肠孤病毒科（包括轮状病毒，这是全世界婴儿腹泻的最常见原因）。我们将比较相同基因在主要肠道病毒和主要非肠道病毒中的进化速率，这将使我们能够对病毒进行同类比较。我们使用的 BEAST 软件采用贝叶斯系统发育合并方法来计算进化率。这种估计的准确性会随着不同的时间尺度而变化，而且我们的一些分析的合并时间也有一个数量级的变化（即，一些数据在 70 年内合并，其他数据在 700 年内合并）。由于许多肠道病毒数据集比非肠道病毒数据集合并得更快，因此将进行额外的控制以确保我们的结果不会因合并时间而产生偏差。我们的工作有可能开辟研究肠组织向性是否在机制上导致 RNA 病毒进化速度更快的研究途径，并强调广泛使用的软件程序中的弱点。