A single amino acid in the polymerase acidic protein determines the pathogenicity of influenza B viruses

Joon Yong Bae, Ilseob Lee, Jin Il Kim, Sehee Park, Kirim Yoo, Miso Park, Gayeong Kim, Mee Sook Park, Joo Yeon Lee, Chun Kang, Kisoon Kim, Man-Seong Park

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3 Citations (Scopus)

Abstract

Influenza B virus (IBV) is one of the human respiratory viruses and one of the targets of seasonal vaccination. However, the bifurcation of two antigenically distinct lineages of IBVs makes it difficult to arrange proper medical countermeasures. Moreover, compared with pathogenicity-related molecular markers known for influenza A virus, little has been known for IBVs. To understand pathogenicity caused by IBVs, we investigated the molecular determinants of IBV pathogenicity in animal models. After serial lung-to-lung passages of Victoria lineage B/Brisbane/60/ 2008 (Vc_BR60) and Yamagata lineage B/Wisconsin/01/2010 (Ym_WI01) viruses in BALB/c mice, we identified the mouse-adapted Vc_BR60 (maVc_BR60) and Ym_WI01 (maYm_WI01) viruses, respectively. To find a molecular clue(s) to the increased pathogenicity of maVc_BR60 and maYm_WI01, we determined their genetic sequences. Several amino acid mutations were identified in the PB2, PB1, PA, BM2, and/or NS1 protein-coding regions, and one concurrent lysine (K)-to-arginine (R) mutation in PA residue 338 (PA K338R) was found in both maVc_BR60 and maYm_WI01 viruses. When analyzed using viruses rescued through reverse genetics, it was shown that PA K338R alone could increase the pathogenicity of both IBVs in mice and viral replication in the respiratory tracts of ferrets. In a subsequent minireplicon assay, the effect of PA K338R was highlighted by the enhancement of viral polymerase complex activity of both Vc_BR60 and Ym_WI01 viruses. These results suggest that the PA K338R mutation may be a molecular determinant of IBV pathogenicity via modulating the viral polymerase function of IBVs.

Original languageEnglish
Article numbere00259-18
JournalJournal of Virology
Volume92
Issue number13
DOIs
Publication statusPublished - 2018 Jul 1

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Keywords

  • Adaptation
  • Influenza B virus
  • Pathogenicity
  • Polymerase

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Bae, J. Y., Lee, I., Kim, J. I., Park, S., Yoo, K., Park, M., Kim, G., Park, M. S., Lee, J. Y., Kang, C., Kim, K., & Park, M-S. (2018). A single amino acid in the polymerase acidic protein determines the pathogenicity of influenza B viruses. Journal of Virology, 92(13), [e00259-18]. https://doi.org/10.1128/JVI.00259-18