ArticleVaccines2025
Attenuating Mutations in Usutu Virus: Towards Understanding Orthoflavivirus Virulence Determinants and Live Attenuated Vaccine Design.
Article in Vaccines, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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7 authors.
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Abstract
BACKGROUND/
objectivesUnderstanding virulence determinants can inform safer and more efficacious live attenuated vaccine design. However, applying this knowledge across related viruses does not always result in conserved phenotypes from similar mutants.
methodsUsing Usutu virus (USUV), an emerging orthoflavivirus spreading through Europe, we assessed whether the attenuating effect of the mutations described for related orthoflaviviruses is conserved. Candidate attenuating mutations were selected based on previous studies in other orthoflaviviruses and incorporated into USUV.
resultsNine variants, with mutations in the USUV envelope, non-structural (NS) proteins NS1, NS2A, or NS4B were stable and selected for further characterisation. The variants with an attenuating phenotype in cell culture were then compared to the wild-type virus in an Ifnar
conclusionsIn addition to improving our understanding of USUV virulence determinants, these results add to a growing body of literature highlighting the most promising mechanisms to target for the design of safe live attenuated vaccines against emerging orthoflaviviruses.
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