Easterbrook Linda, Dong Xiaofeng, Smith Jack, Fotheringham Susan, Kempster Sarah, Hartley Catherine, Prince Tessa, Graham Victoria, Kennedy Emma, Findlay-Wilson Stephen, Crossley Lucy, Hewson Roger, Almond Neil, Hiscox Julian A, Dowall Stuart
UK Health Security Agency (UKHSA), Porton Down, Salisbury, SP4 0JG, Wiltshire, UK.
Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, L3 5RF, UK.
BMC Genomics. 2025 May 15;26(1):489. doi: 10.1186/s12864-025-11666-y.
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.
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.
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.
拉沙病毒（LASV）可引发人类严重出血热，据估计，在流行地区每年有10万至30万例感染，约5000人死亡。其天然宿主是多乳鼠，但通过人畜共患病传播，人类成为偶然宿主。定期爆发的疫情持续给公共卫生系统带来压力，该病毒引发医院感染的能力对医护人员构成风险。令人担忧的是，更大规模的疫情爆发以及LASV传入新地区的情况将会加剧，包括适应新的哺乳动物宿主的风险。
为评估LASV在适应新宿主过程中的基因变化，采用了豚鼠感染模型。用从细胞培养物中培养的LASV毒株进行初次感染，仅导致轻度或亚临床疾病。为研究未接触过该病毒的动物的易感性，病毒进行了连续传代，在疾病进展过程中临床症状加重，最终导致严重疾病。采用RNA测序和一致性图谱分析方法评估每一代动物LASV基因组中的核苷酸变化。
在适应豚鼠的过程中，未出现显著的新突变。相反，观察到L片段的两个基因受到选择压力，导致其在传代过程中在基因组群体中的频率增加。
