N460S in PB2 and I163T in nucleoprotein synergistically enhance the viral replication and pathogenicity of influenza B virus.

ABSTRACT: Influenza B viruses (IBVs), though often overshadowed by influenza A viruses (IAVs), remain a significant global public health concern, particularly during seasons when they predominate. However, the molecular mechanisms underlying IBV pathogenicity remain largely unknown. In this study, we identified two amino acid substitutions, PB2-N460S and NP-I163T, from IBV clinical isolates with distinct replication and pathogenicity profiles. Using reverse genetics, we generated recombinant IBV viruses to evaluate the impact of these substitutions. In vitro and in vivo infections revealed that viral replication and pathogenicity were not significantly affected by either substitution alone but were substantially enhanced when both substitutions occurred together. Lung transcriptomics in mice infecte

SUBMITTER: Wang Y 

PROVIDER: S-EPMC12431660 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature