关键词: multi-strain dynamics mutations phylogenetic analysis porcine reproductive and respiratory syndrome virus principal component analyses viral population dynamics whole genome

来  源:   DOI:10.3390/vaccines9060608   PDF(Sci-hub)   PDF(Pubmed)

Abstract:
The genetic diversity and frequent emergence of novel genetic variants of porcine reproductive and respiratory syndrome virus type-2 (PRRSV) hinders control efforts, yet drivers of macro-evolutionary patterns of PRRSV remain poorly documented. Utilizing a comprehensive database of >20,000 orf5 sequences, our objective was to classify variants according to the phylogenetic structure of PRRSV co-circulating in the U.S., quantify evolutionary dynamics of sub-lineage emergence, and describe potential antigenic differences among sub-lineages. We subdivided the most prevalent lineage (Lineage 1, accounting for approximately 60% of available sequences) into eight sub-lineages. Bayesian coalescent SkyGrid models were used to estimate each sub-lineage\'s effective population size over time. We show that a new sub-lineage emerged every 1 to 4 years and that the time between emergence and peak population size was 4.5 years on average (range: 2-8 years). A pattern of sequential dominance of different sub-lineages was identified, with a new dominant sub-lineage replacing its predecessor approximately every 3 years. Consensus amino acid sequences for each sub-lineage differed in key GP5 sites related to host immunity, suggesting that sub-lineage turnover may be linked to immune-mediated competition. This has important implications for understanding drivers of genetic diversity and emergence of new PRRSV variants in the U.S.
摘要:
猪繁殖与呼吸综合征病毒2型(PRRSV)的遗传多样性和新遗传变异的频繁出现阻碍了控制努力,然而PRRSV宏观进化模式的驱动因素仍然缺乏文献记载.利用>20,000orf5序列的综合数据库,我们的目标是根据PRRSV在美国共同传播的系统发育结构对变异进行分类,量化亚谱系出现的进化动力学,并描述亚谱系之间潜在的抗原差异。我们将最普遍的谱系(谱系1,约占可用序列的60%)细分为八个子谱系。贝叶斯合并SkyGrid模型用于估计每个子谱系随时间的有效种群规模。我们表明,每1到4年出现一个新的亚谱系,从出现到人口高峰之间的时间平均为4.5年(范围:2-8年)。确定了不同子谱系的顺序优势模式,大约每3年有一个新的占主导地位的子血统取代它的前身。每个亚谱系的共有氨基酸序列在与宿主免疫相关的关键GP5位点不同,这表明亚谱系更替可能与免疫介导的竞争有关。这对理解遗传多样性的驱动因素和美国新PRRSV变异的出现具有重要意义
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