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评估全基因组测序在追踪牛呼吸道合胞体病毒实验感染和自然暴发传播途径中的潜力。

Evaluating the potential of whole-genome sequencing for tracing transmission routes in experimental infections and natural outbreaks of bovine respiratory syncytial virus.

机构信息

School of Biodiversity, One Health and Veterinary Medicine, University of Glasgow, Glasgow, UK.

HPIG. Unit of Ruminant Medicine. Department of Clinical Sciences, Swedish University of Agricultural Sciences (SLU), Uppsala, Sweden.

出版信息

Vet Res. 2022 Dec 12;53(1):107. doi: 10.1186/s13567-022-01127-9.

DOI:10.1186/s13567-022-01127-9
PMID:36510312
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9746130/
Abstract

Bovine respiratory syncytial virus (BRSV) is a major cause of respiratory disease in cattle. Genomic sequencing can resolve phylogenetic relationships between virus populations, which can be used to infer transmission routes and potentially inform the design of biosecurity measures. Sequencing of short (<2000 nt) segments of the 15 000-nt BRSV genome has revealed geographic and temporal clustering of BRSV populations, but insufficient variation to distinguish viruses collected from herds infected close together in space and time. This study investigated the potential for whole-genome sequencing to reveal sufficient genomic variation for inferring transmission routes between herds. Next-generation sequencing (NGS) data were generated from experimental infections and from natural outbreaks in Jämtland and Uppsala counties in Sweden. Sufficient depth of coverage for analysis of consensus and sub-consensus sequence diversity was obtained from 47 to 20 samples respectively. Few (range: 0-6 polymorphisms across the six experiments) consensus-level polymorphisms were observed along experimental transmissions. A much higher level of diversity (146 polymorphic sites) was found among the consensus sequences from the outbreak samples. The majority (144/146) of polymorphisms were between rather than within counties, suggesting that consensus whole-genome sequences show insufficient spatial resolution for inferring direct transmission routes, but might allow identification of outbreak sources at the regional scale. By contrast, within-sample diversity was generally higher in the experimental than the outbreak samples. Analyses to infer known (experimental) and suspected (outbreak) transmission links from within-sample diversity data were uninformative. In conclusion, analysis of the whole-genome sequence of BRSV from experimental samples discriminated between circulating isolates from distant areas, but insufficient diversity was observed between closely related isolates to aid local transmission route inference.

摘要

牛呼吸道合胞体病毒(BRSV)是牛呼吸道疾病的主要原因。基因组测序可以解决病毒群体之间的系统发育关系,这可以用来推断传播途径,并可能为生物安全措施的设计提供信息。对 15000nt BRSV 基因组的短(<2000nt)片段进行测序揭示了 BRSV 种群的地理和时间聚类,但不足以区分从空间和时间上紧密相关的畜群中收集的病毒。本研究探讨了全基因组测序是否有可能揭示足够的基因组变异,以推断畜群之间的传播途径。从瑞典耶姆特兰和乌普萨拉县的实验感染和自然暴发中生成了下一代测序(NGS)数据。分别从 47 到 20 个样本中获得了足够的覆盖深度,用于分析共识和亚共识序列多样性。在实验传播中观察到的共识水平多态性很少(6 次实验中跨 6 个的范围为 0-6 个多态性)。在暴发样本的共识序列中发现了更高水平的多样性(146 个多态性位点)。大多数(144/146)多态性位于县之间而不是县内,这表明共识全基因组序列对于推断直接传播途径的空间分辨率不足,但可能允许在区域范围内识别暴发源。相比之下,实验样本中的内样本多样性通常高于暴发样本。从内样本多样性数据推断已知(实验)和疑似(暴发)传播联系的分析没有提供信息。总之,对来自实验样本的 BRSV 全基因组序列的分析可以区分来自遥远地区的循环分离株,但在密切相关的分离株之间观察到的多样性不足,无法帮助推断当地的传播途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/978d/9746130/8fb306ad311d/13567_2022_1127_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/978d/9746130/f8cdc9290406/13567_2022_1127_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/978d/9746130/8fb306ad311d/13567_2022_1127_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/978d/9746130/f8cdc9290406/13567_2022_1127_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/978d/9746130/9637bf093e1a/13567_2022_1127_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/978d/9746130/a13aab66ff64/13567_2022_1127_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/978d/9746130/91e4f825a482/13567_2022_1127_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/978d/9746130/0159b83e7db1/13567_2022_1127_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/978d/9746130/8fb306ad311d/13567_2022_1127_Fig6_HTML.jpg

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