Contemporary Victoria and Yamagata Influenza B Viruses Elicit Lineage-Specific Differences in Innate Immunity

Abstract

The two influenza B virus (FLUBV) lineages, Victoria and Yamagata, have continued to diverge since their separation in the 1970s, resulting in distinct antigenic characteristics and differences in immunity and cross-protection. Human epidemiological observations and experimental studies have identified lineage-specific differences in adaptive immune responses elicited by contemporary viruses, suggesting that innate immune signaling may contribute to these divergent outcomes. To understand in-depth immunity to contemporary influenza B viruses, we compared viral replication, cytokine production, gene expression, and cellular tropism following infection with representative Victoria- and Yamagata-lineage viruses. We found that, despite broadly similar cytokine profiles in the ferret upper respiratory tract, the two lineages exhibited distinct innate immune kinetics. Yamagata viruses induced rapid early expression of antiviral and inflammatory genes, including SOCS1 and multiple interferon-stimulated genes, whereas Victoria viruses displayed delayed innate immune activation accompanied by greater viral replication. Consistent with the ferret data, Yamagata viruses also induced elevated SOCS1 expression in human PBMCs early after infection. In addition, Yamagata viruses exhibited broader cellular tropism, infecting a wider range of immune cell populations than Victoria viruses. Together, these findings demonstrate that contemporary influenza B virus lineages distinctly engage the host immune system and provide new insight into how lineage-specific innate immune responses may contribute to differences in immunity, cross-protection, and the divergent evolutionary trajectories of Victoria and Yamagata viruses

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BibTeX

@misc{page2026contemporary,
  title = {{Contemporary Victoria and Yamagata Influenza B Viruses Elicit Lineage-Specific Differences in Innate Immunity}},
  author = {C. K. Page and V. Zyulina and W. Zhang and G. Geiger and V. Dhamapurkar and D. Bernal- Rubio and D. Guerrero and S. D. Ray and J. D. Shepard and A. Fernandez-Sesma and K. Kedzierska and S. M. Tompkins},
  howpublished = {bioRxiv},
  year = {2026},
  month = sep,
  doi = {10.64898/2026.09.17.752522},
  url = {https://www.biorxiv.org/content/10.64898/2026.09.17.752522v1},
  note = {CC BY},
}

RIS

TY  - UNPB
TI  - Contemporary Victoria and Yamagata Influenza B Viruses Elicit Lineage-Specific Differences in Innate Immunity
AU  - C. K. Page
AU  - V. Zyulina
AU  - W. Zhang
AU  - G. Geiger
AU  - V. Dhamapurkar
AU  - D. Bernal- Rubio
AU  - D. Guerrero
AU  - S. D. Ray
AU  - J. D. Shepard
AU  - A. Fernandez-Sesma
AU  - K. Kedzierska
AU  - S. M. Tompkins
PY  - 2026
DA  - 2026/09/17
PB  - bioRxiv
DO  - 10.64898/2026.09.17.752522
UR  - https://www.biorxiv.org/content/10.64898/2026.09.17.752522v1
AB  - The two influenza B virus (FLUBV) lineages, Victoria and Yamagata, have continued to diverge since their separation in the 1970s, resulting in distinct antigenic characteristics and differences in immunity and cross-protection. Human epidemiological observations and experimental studies have identified lineage-specific differences in adaptive immune responses elicited by contemporary viruses, suggesting that innate immune signaling may contribute to these divergent outcomes. To understand in-depth immunity to contemporary influenza B viruses, we compared viral replication, cytokine production, gene expression, and cellular tropism following infection with representative Victoria- and Yamagata-lineage viruses. We found that, despite broadly similar cytokine profiles in the ferret upper respiratory tract, the two lineages exhibited distinct innate immune kinetics. Yamagata viruses induced rapid early expression of antiviral and inflammatory genes, including SOCS1 and multiple interferon-stimulated genes, whereas Victoria viruses displayed delayed innate immune activation accompanied by greater viral replication. Consistent with the ferret data, Yamagata viruses also induced elevated SOCS1 expression in human PBMCs early after infection. In addition, Yamagata viruses exhibited broader cellular tropism, infecting a wider range of immune cell populations than Victoria viruses. Together, these findings demonstrate that contemporary influenza B virus lineages distinctly engage the host immune system and provide new insight into how lineage-specific innate immune responses may contribute to differences in immunity, cross-protection, and the divergent evolutionary trajectories of Victoria and Yamagata viruses
ER  -

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