Characterization of the glycoproteins of fish and amphibian influenza B-like viruses

Gagandeep Singh; Jiachen Huang; Disha Bhavsar; Kirill Vasilev; James A Ferguson; Geert-Jan Boons; Viviana Simon; Robert Paul de Vries; Julianna Han; Andrew B Ward; Florian Krammer

doi:10.1126/sciadv.ady8610

Characterization of the glycoproteins of fish and amphibian influenza B-like viruses

Gagandeep Singh
, Jiachen Huang
, Disha Bhavsar
, Kirill Vasilev
, James A Ferguson
, Geert-Jan Boons
, Viviana Simon
, Robert Paul de Vries
, Julianna Han
, Andrew B Ward
, Florian Krammer^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Influenza-like virus sequences previously identified in fish and amphibians cluster as a sister clade of influenza B viruses but remain largely uncharacterized. We demonstrate that salamander influenza-like virus (SILV) hemagglutinin (HA) is functionally divergent from influenza B virus HA and does not bind to α2,3- and α2,6-linked sialic acids. However, the HAs of Siamese algae-eater influenza-like virus (SAEILV) and chum salmon influenza-like virus (CSILV) bind to α2,3-linked sialic acid. Furthermore, SAEILV HA binds to sialyated Lewis X, is activated by human airway enzymes, and is fusogenic over a broad pH range. SAEILV neuraminidase (NA) has a highly conserved active site and a similar structure to other known NAs. We also determined the cryo–electron microscopy structure of the HA of a previously described virus from the same sister clade, the Wuhan spiny eel influenza virus (WSEIV). No cross-reactive antibodies against these HAs or NAs were found in human serum, suggesting that humans are immunologically naïve to these viruses.

Original language	English
Article number	eady8610
Number of pages	15
Journal	Science advances
Volume	11
Issue number	34
DOIs	https://doi.org/10.1126/sciadv.ady8610
Publication status	Published - 22 Aug 2025

Bibliographical note

Publisher Copyright:
Copyright © 2025 The Authors, some rights reserved.

Funding

We would like to thank E. Holmes at The University of Sydney for inspiring us to perform this study and for making the sequence information available. We appreciate the study participants for their generosity and willingness to enroll and donate samples for our research purpose. Special thanks go to the teams of the PARIS study and the Personalized Virology Initiative for sharing biospecimen and metadata from study participants.Work in the Krammer laboratory was funded by the NIAID Centers of Excellence for Influenza Research and Response (CEIRR; 75N93021C00014, F.K.) and an institutional fund. Work in the Ward laboratory was funded by the NIAID Collaborative Influenza Vaccine Innovation Centers (CIVIC; 75N39019C00051, A.W.). G.-J.B. is funded by the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH) under award number R01 AI165692.

Funders	Funder number
University of Sydney
NIAID Centers of Excellence for Influenza Research and Response
National Institute of Allergy and Infectious Diseases
CEIRR	75N93021C00014, 75N39019C00051
National Institutes of Health	R01 AI165692

Access to Document

10.1126/sciadv.ady8610Licence: CC BY-NC

Characterization of the glycoproteins of fish and amphibian influenza B–like virusesFinal published version, 1.56 MBLicence: CC BY-NC

Cite this

@article{596de9855efc4d73ba26be9ebcba7d76,

title = "Characterization of the glycoproteins of fish and amphibian influenza B-like viruses",

abstract = "Influenza-like virus sequences previously identified in fish and amphibians cluster as a sister clade of influenza B viruses but remain largely uncharacterized. We demonstrate that salamander influenza-like virus (SILV) hemagglutinin (HA) is functionally divergent from influenza B virus HA and does not bind to α2,3- and α2,6-linked sialic acids. However, the HAs of Siamese algae-eater influenza-like virus (SAEILV) and chum salmon influenza-like virus (CSILV) bind to α2,3-linked sialic acid. Furthermore, SAEILV HA binds to sialyated Lewis X, is activated by human airway enzymes, and is fusogenic over a broad pH range. SAEILV neuraminidase (NA) has a highly conserved active site and a similar structure to other known NAs. We also determined the cryo{\textendash}electron microscopy structure of the HA of a previously described virus from the same sister clade, the Wuhan spiny eel influenza virus (WSEIV). No cross-reactive antibodies against these HAs or NAs were found in human serum, suggesting that humans are immunologically na{\"i}ve to these viruses.",

author = "Gagandeep Singh and Jiachen Huang and Disha Bhavsar and Kirill Vasilev and Ferguson, \{James A\} and Geert-Jan Boons and Viviana Simon and \{de Vries\}, \{Robert Paul\} and Julianna Han and Ward, \{Andrew B\} and Florian Krammer",

note = "Publisher Copyright: Copyright {\textcopyright} 2025 The Authors, some rights reserved.",

year = "2025",

month = aug,

day = "22",

doi = "10.1126/sciadv.ady8610",

language = "English",

volume = "11",

journal = "Science advances",

issn = "2375-2548",

publisher = "American Association for the Advancement of Science",

number = "34",

}

TY - JOUR

T1 - Characterization of the glycoproteins of fish and amphibian influenza B-like viruses

AU - Singh, Gagandeep

AU - Huang, Jiachen

AU - Bhavsar, Disha

AU - Vasilev, Kirill

AU - Ferguson, James A

AU - Boons, Geert-Jan

AU - Simon, Viviana

AU - de Vries, Robert Paul

AU - Han, Julianna

AU - Ward, Andrew B

AU - Krammer, Florian

PY - 2025/8/22

Y1 - 2025/8/22

N2 - Influenza-like virus sequences previously identified in fish and amphibians cluster as a sister clade of influenza B viruses but remain largely uncharacterized. We demonstrate that salamander influenza-like virus (SILV) hemagglutinin (HA) is functionally divergent from influenza B virus HA and does not bind to α2,3- and α2,6-linked sialic acids. However, the HAs of Siamese algae-eater influenza-like virus (SAEILV) and chum salmon influenza-like virus (CSILV) bind to α2,3-linked sialic acid. Furthermore, SAEILV HA binds to sialyated Lewis X, is activated by human airway enzymes, and is fusogenic over a broad pH range. SAEILV neuraminidase (NA) has a highly conserved active site and a similar structure to other known NAs. We also determined the cryo–electron microscopy structure of the HA of a previously described virus from the same sister clade, the Wuhan spiny eel influenza virus (WSEIV). No cross-reactive antibodies against these HAs or NAs were found in human serum, suggesting that humans are immunologically naïve to these viruses.

AB - Influenza-like virus sequences previously identified in fish and amphibians cluster as a sister clade of influenza B viruses but remain largely uncharacterized. We demonstrate that salamander influenza-like virus (SILV) hemagglutinin (HA) is functionally divergent from influenza B virus HA and does not bind to α2,3- and α2,6-linked sialic acids. However, the HAs of Siamese algae-eater influenza-like virus (SAEILV) and chum salmon influenza-like virus (CSILV) bind to α2,3-linked sialic acid. Furthermore, SAEILV HA binds to sialyated Lewis X, is activated by human airway enzymes, and is fusogenic over a broad pH range. SAEILV neuraminidase (NA) has a highly conserved active site and a similar structure to other known NAs. We also determined the cryo–electron microscopy structure of the HA of a previously described virus from the same sister clade, the Wuhan spiny eel influenza virus (WSEIV). No cross-reactive antibodies against these HAs or NAs were found in human serum, suggesting that humans are immunologically naïve to these viruses.

UR - https://www.scopus.com/pages/publications/105013963081

U2 - 10.1126/sciadv.ady8610

DO - 10.1126/sciadv.ady8610

M3 - Article

SN - 2375-2548

VL - 11

JO - Science advances

JF - Science advances

IS - 34

M1 - eady8610

ER -

Characterization of the glycoproteins of fish and amphibian influenza B-like viruses

Abstract

Bibliographical note

Funding

Access to Document

Other files and links

Fingerprint

Cite this