Genomic changes of Lassa virus associated with mammalian host adaptation.

IF 3.5 2区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Linda Easterbrook, Xiaofeng Dong, Jack Smith, Susan Fotheringham, Sarah Kempster, Catherine Hartley, Tessa Prince, Victoria Graham, Emma Kennedy, Stephen Findlay-Wilson, Lucy Crossley, Roger Hewson, Neil Almond, Julian A Hiscox, Stuart Dowall
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引用次数: 0

Abstract

Background: Lassa virus (LASV) causes a severe haemorrhagic fever in humans, with estimates of 100,000 to 300,000 infections annually in endemic regions and accounting for around 5000 deaths. The natural reservoir is the Mastomys rat, but through zoonotic transmissions humans are accidental hosts. Regular outbreaks continue to exert pressures on public health systems, with its ability to cause nosocomial infections posing risks to healthcare workers. It is a concern that larger outbreaks and introduction of LASV to new territories will intensify, including risk of adaptation to new mammalian host reservoirs.

Results: To evaluate genetic changes in LASV during adaptation to a new host, a guinea pig model of infection was utilised. Initial infection with LASV stocks cultured from cell culture resulted in only mild or subclinical disease. To study the susceptibility in naïve animals, the virus was serially passaged which increased clinical signs during disease progression ultimately resulting in severe disease. An RNAseq and consensus mapping approach was undertaken to evaluate nucleotide changes in LASV genome from each animal at each passage.

Conclusions: During adaptation to guinea pigs, no significant new mutations occurred. Instead, a selection pressure on two genes of the L segment was observed resulting in their increased frequency in the genome population during passaging.

与哺乳动物宿主适应相关的拉沙病毒基因组变化
背景:拉沙病毒(LASV)在人类中引起严重的出血热,估计在流行地区每年有10万至30万人感染,造成约5000人死亡。自然宿主是Mastomys鼠,但通过人畜共患病传播,人类是意外宿主。定期暴发继续对公共卫生系统造成压力,它有能力引起医院感染,对卫生保健工作者构成风险。令人关切的是,LASV的大规模暴发和向新领土的传入将会加剧,包括适应新的哺乳动物宿主宿主的风险。结果:为了评估LASV在适应新宿主过程中的遗传变化,采用了豚鼠感染模型。最初感染由细胞培养的LASV存量只导致轻微或亚临床疾病。为了研究naïve动物的易感性,对病毒进行了连续传代,增加了疾病进展期间的临床症状,最终导致严重疾病。采用RNAseq和共识作图方法来评估每只动物LASV基因组在每次传代时的核苷酸变化。结论:在对豚鼠的适应过程中,没有发生明显的新突变。相反,在传代过程中,观察到L段的两个基因的选择压力导致它们在基因组群体中的频率增加。
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来源期刊
BMC Genomics
BMC Genomics 生物-生物工程与应用微生物
CiteScore
7.40
自引率
4.50%
发文量
769
审稿时长
6.4 months
期刊介绍: BMC Genomics is an open access, peer-reviewed journal that considers articles on all aspects of genome-scale analysis, functional genomics, and proteomics. BMC Genomics is part of the BMC series which publishes subject-specific journals focused on the needs of individual research communities across all areas of biology and medicine. We offer an efficient, fair and friendly peer review service, and are committed to publishing all sound science, provided that there is some advance in knowledge presented by the work.
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