Attenuating Mutations in Usutu Virus: Towards Understanding Orthoflavivirus Virulence Determinants and Live Attenuated Vaccine Design.

ABSTRACT:

Background/objectives

Understanding 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.

Methods

Using 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.

Results

Nine 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

SUBMITTER: Duyvestyn JM 

PROVIDER: S-EPMC12115599 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature