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Molecular Evolution of Herpes Simplex Virus 2 Complete Genomes: Comparison between Primary and Recurrent Infections
Journal of Virology ( IF 5.4 ) Pub Date : 2017-12-01 , DOI: 10.1128/jvi.00942-17
Miguel A Minaya 1 , Travis L Jensen 2 , Johannes B Goll 2 , Maria Korom 3 , Sree H Datla 3 , Robert B Belshe 4 , Lynda A Morrison 1, 4
Affiliation  

Herpes simplex virus 1 (HSV-1) and HSV-2 are large, double-stranded DNA viruses that cause lifelong persistent infections characterized by periods of quiescence and recurrent disease. How HSV evolves within an infected individual experiencing multiple episodes of recurrent disease over time is not known. We determined the genome sequences of viruses isolated from two subjects in the Herpevac Trial for Women who experienced primary HSV-2 genital disease and compared them with sequences of viruses isolated from the subsequent fifth or sixth episode of recurrent disease in the same individuals. Each of the HSV-2 genome sequences was initially obtained using next-generation sequencing and completed with Sanger sequencing. Polymorphisms over the entire genomes were mapped, and amino acid variants resulting from nonsynonymous changes were analyzed based on the secondary and tertiary structures of a previously crystallized protein. A phylogenetic reconstruction was used to assess relationships among the four HSV-2 samples, other North American sequences, and reference sequences. Little genetic drift was detected in viruses shed by the same subjects following repeated reactivation events, suggesting strong selective pressure on the viral genome to maintain sequence fidelity during reactivations from its latent state within an individual host. Our results also demonstrate that some primary HSV-2 isolates from North America more closely resemble the HG52 laboratory strain from Scotland than the low-passage-number clinical isolate SD90e from South Africa or laboratory strain 333. Thus, one of the sequences reported here would be a logical choice as a reference strain for inclusion in future studies of North American HSV-2 isolates.

IMPORTANCE The extent to which the HSV-2 genome evolves during multiple episodes of reactivation from its latent state within an infected individual is not known. We used next-generation sequencing techniques to determine whole-genome sequences of four viral samples from two subjects in the Herpevac Trial. The sequence of each subject's well-documented primary isolate was compared with the sequence of the isolate from their fifth or sixth episode of recurrent disease. Only 19 genetic polymorphisms unique to the primary or recurrent isolate were identified, 10 in subject A and 9 in subject B. These observations indicate remarkable genetic conservation between primary and recurrent episodes of HSV-2 infection and imply that strong selection pressures exist to maintain the fidelity of the viral genome during repeated reactivations from its latent state. The genome conservation observed also has implications for the potential success of a therapeutic vaccine.



中文翻译:

单纯疱疹病毒2个完整基因组的分子进化:原发性和复发性感染之间的比较。

单纯疱疹病毒1(HSV-1)和HSV-2是大型的双链DNA病毒,会导致终身持续感染,其特征是处于静止期和复发性疾病。随着时间的推移,经历多次复发性疾病发作的受感染个体中HSV的进化方式尚不清楚。我们确定了在患有原发性HSV-2生殖器疾病的女性Herpevac试验中从两名受试者中分离出的病毒的基因组序列,并将其与从同一个体中继发于第五或第六次复发性疾病中分离出的病毒序列进行了比较。每个HSV-2基因组序列最初都是使用下一代测序获得的,并通过Sanger测序完成。绘制了整个基因组的多态性图,基于先前结晶的蛋白质的二级和三级结构,对由非同义变化产生的氨基酸变体和氨基酸变体进行了分析。系统发育重建用于评估四个HSV-2样本,其他北美序列和参考序列之间的关系。在重复激活事件之后,同一受试者散发出的病毒中几乎没有检测到遗传漂移,这表明在从单个宿主内的潜伏状态恢复激活过程中,病毒基因组具有强大的选择性压力以保持序列保真度。我们的研究结果还表明,与来自南非的低通过次数临床隔离株SD90e或来自实验室的333菌株相比,来自北美的一些主要HSV-2分离株与来自苏格兰的HG52实验室菌株更相似。

重要性HSV-2基因组在多次复活期间从受感染个体内的潜伏状态演变的程度尚不清楚。在Herpevac试验中,我们使用了下一代测序技术来确定来自两个受试者的四个病毒样品的全基因组序列。将每个受试者的有据可查的主要分离株的序列与他们第五或第六次复发性疾病的分离株的序列进行比较。仅鉴定出19种主要或复发分离株特有的遗传多态性,受试者A中为10种,受试者B中为9种。这些观察结果表明,HSV-2感染的初次发作与复发之间具有显着的遗传保守性,这表明存在强大的选择压力来维持病毒基因组从潜在状态反复激活过程中的保真度。

更新日期:2017-11-15
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