Genomic changes of Lassa virus associated with mammalian host adaptation
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...
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BMC
2025-05-01
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| Online Access: | https://doi.org/10.1186/s12864-025-11666-y |
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| author | 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 |
| author_facet | 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 |
| author_sort | Linda Easterbrook |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-c35c5839ac5743b3b066fa2ff238536a |
| institution | Kabale University |
| issn | 1471-2164 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Genomics |
| spelling | doaj-art-c35c5839ac5743b3b066fa2ff238536a2025-08-20T03:53:57ZengBMCBMC Genomics1471-21642025-05-0126111010.1186/s12864-025-11666-yGenomic changes of Lassa virus associated with mammalian host adaptationLinda Easterbrook0Xiaofeng Dong1Jack Smith2Susan Fotheringham3Sarah Kempster4Catherine Hartley5Tessa Prince6Victoria Graham7Emma Kennedy8Stephen Findlay-Wilson9Lucy Crossley10Roger Hewson11Neil Almond12Julian A. Hiscox13Stuart Dowall14UK Health Security Agency (UKHSA)Institute of Infection, Veterinary and Ecological Sciences, University of LiverpoolUK Health Security Agency (UKHSA)UK Health Security Agency (UKHSA)Medicines and Healthcare products Regulatory Agency (MHRA)Institute of Infection, Veterinary and Ecological Sciences, University of LiverpoolInstitute of Infection, Veterinary and Ecological Sciences, University of LiverpoolUK Health Security Agency (UKHSA)UK Health Security Agency (UKHSA)UK Health Security Agency (UKHSA)UK Health Security Agency (UKHSA)UK Health Security Agency (UKHSA)Medicines and Healthcare products Regulatory Agency (MHRA)Institute of Infection, Veterinary and Ecological Sciences, University of LiverpoolUK Health Security Agency (UKHSA)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.https://doi.org/10.1186/s12864-025-11666-yLassa virusAdaptationPassageMutationChanges |
| spellingShingle | 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 Genomic changes of Lassa virus associated with mammalian host adaptation BMC Genomics Lassa virus Adaptation Passage Mutation Changes |
| title | Genomic changes of Lassa virus associated with mammalian host adaptation |
| title_full | Genomic changes of Lassa virus associated with mammalian host adaptation |
| title_fullStr | Genomic changes of Lassa virus associated with mammalian host adaptation |
| title_full_unstemmed | Genomic changes of Lassa virus associated with mammalian host adaptation |
| title_short | Genomic changes of Lassa virus associated with mammalian host adaptation |
| title_sort | genomic changes of lassa virus associated with mammalian host adaptation |
| topic | Lassa virus Adaptation Passage Mutation Changes |
| url | https://doi.org/10.1186/s12864-025-11666-y |
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