Andersen et al. used Illumina sequencing to assemble 183 LASV genomes from clinical samples collected in Sierra Leone and Nigeria, together with 2 LASV genomes from laboratory isolates and 11 LASV genomes from field samples of its rodent reservoir, Mastomys natalensis. A phylogenetic analysis showed that LASV was far more genetically diverse than EBOV, with <75% sequence conservation compared with >97% in EBOV. Importantly, the phylogeny did not cluster by host, which suggests that human-to-human transmission of LASV is negligible (or non-existent). LASV genomes were most diverse in present-day Nigeria, and the authors calculated that the last common ancestor of extant LASV strains was probably located here ∼1000 years ago. This suggests that LASV is a long-standing human pathogen; by contrast, all sequenced human isolates of EBOV share a common ancestor within the past 50 years.
As might be expected for a more long-standing human pathogen, the codons in LASV genomes were better adapted to the tRNA repertoire of human hosts than those in EBOV genomes. Interestingly, codon usage in LASV genomes from Sierra Leone was significantly better adapted than in LASV genomes from Nigeria, which suggests that a burst of codon adaptation has accompanied the spread of LASV across West Africa. Viral genome abundance and infection fatality rate were also significantly higher in patients from Sierra Leone than in those from Nigeria, suggesting that accelerated codon adaptation might have boosted viral replicative activity. However, unexpectedly, Sierra Leonean LASV sequences were translated less efficiently than those from Nigeria in an in vitro assay, and so it is unclear whether these changes in codon usage are important for virus productivity.
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