Genomic Analysis of the Vaccinia Virus Strain Variants Found in Dryvax Vaccine
Genomic Analysis of the Vaccinia Virus Strain Variants Found in Dryvax Vaccine
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DOI：
10.1128/jvi.05779-11
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发表时间：
2011-12-01
影响因子：
5.4
通讯作者：
Evans, David H.
中科院分区：
文献类型：
--
作者：
Qin, Li;Upton, Chris;Evans, David H.
使用不同形式的牛痘病毒疫苗根除了天花。其中之一是Dryvax，一种源自纽约市卫生局菌株的小牛淋巴疫苗。我们使用基因组测序技术来检查Dryvax样本中存在的病毒种群的遗传多样性。这些研究表明，与端粒相比，这些病毒的保守核心显示出较低水平的序列变异。然而，尽管正痘病毒的末端在遗传上比核心更具可塑性，但在我们和其他人已经测序的11个基因组和4个基因组中，仍然有许多端粒基因作为完整的开放阅读框架保守。这些基因中的大多数可能调节炎症。我们的测序还发现了一种突变的进化模式，一些基因通过随机分类突变而高度碎片化(例如，M1L)，而另一些基因在大多数病毒中是完整的，但在个别毒株中已被破坏(例如，DPP17株的I4L)。超过85%的插入和缺失突变与重复有关，并发现了一种罕见的新分离株，其右侧端粒存在较大的缺失。所有这些毒株都聚集在树状图上，与它们的来源一致，但令人惊讶的是，它们也含有马痘病毒。然而，这些病毒也表现出重组体特有的多态位点的“斑块”模式。在一瓶Dryvax中检测到的遗传多样性比天花病毒主要株和次要株之间的遗传多样性更多，我们的研究强调了繁殖方法如何影响正痘病毒种群的遗传学。
Smallpox was eradicated using variant forms of vaccinia virus-based vaccines. One of these was Dryvax, a calf lymph vaccine derived from the New York City Board of Health strain. We used genome-sequencing technology to examine the genetic diversity of the population of viruses present in a sample of Dryvax. These studies show that the conserved cores of these viruses exhibit a lower level of sequence variation than do the telomeres. However, even though the ends of orthopoxviruses are more genetically plastic than the cores, there are still many telomeric genes that are conserved as intact open reading frames in the 11 genomes that we, and 4 genomes that others, have sequenced. Most of these genes likely modulate inflammation. Our sequencing also detected an evolving pattern of mutation, with some genes being highly fragmented by randomly assorting mutations (e. g., M1L), while other genes are intact in most viruses but have been disrupted in individual strains (e. g., I4L in strain DPP17). Over 85% of insertion and deletion mutations are associated with repeats, and a rare new isolate bearing a large deletion in the right telomere was identified. All of these strains cluster in dendrograms consistent with their origin but which also surprisingly incorporate horsepox virus. However, these viruses also exhibit a "patchy" pattern of polymorphic sites characteristic of recombinants. There is more genetic diversity detected within a vial of Dryvax than between variola virus major and minor strains, and our study highlights how propagation methods affect the genetics of orthopoxvirus populations.