Functionality of the putative surface glycoproteins of the Wuhan spiny eel influenza virus

Guha Asthagiri Arunkumar, Disha Bhavsar, Tiehai Li, Shirin Strohmeier, Veronika Chromikova, Fatima Amanat, Mehman Bunyatov, Patrick C. Wilson, Ali H. Ellebedy, Geert Jan Boons, Viviana Simon, Robert P. de Vries, Florian Krammer*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

A panel of influenza virus-like sequences were recently documented in fish and amphibians. Of these, the Wuhan spiny eel influenza virus (WSEIV) was found to phylogenetically cluster with influenza B viruses as a sister clade. Influenza B viruses have been documented to circulate only in humans, with certain virus isolates found in harbor seals. It is therefore interesting that a similar virus was potentially found in fish. Here we characterize the putative hemagglutinin (HA) and neuraminidase (NA) surface glycoproteins of the WSEIV. Functionally, we show that the WSEIV NA-like protein has sialidase activity comparable to B/Malaysia/2506/2004 influenza B virus NA, making it a bona fide neuraminidase that is sensitive to NA inhibitors. We tested the functionality of the HA by addressing the receptor specificity, stability, preferential airway protease cleavage, and fusogenicity. We show highly specific binding to monosialic ganglioside 2 (GM2) and fusogenicity at a range of different pH conditions. In addition, we found limited antigenic conservation of the WSEIV HA and NA relative to the B/Malaysia/2506/2004 virus HA and NA. In summary, we perform a functional and antigenic characterization of the glycoproteins of WSEIV to assess if it is indeed a bona fide influenza virus potentially circulating in ray-finned fish.

Original languageEnglish
Article number6161
Pages (from-to)1-12
JournalNature Communications
Volume12
Issue number1
DOIs
Publication statusPublished - 25 Oct 2021

Bibliographical note

Funding Information:
We would like to thank Andrew Duty and Tom Moran at the Department of Microbiology at the Icahn School of Medicine at Mount Sinai for letting us use their BLI device. We would also like to thank Edward Holmes at The University of Sidney for inspiring us to perform this study and for making the sequence information available. This work was partially funded by NIAID CEIRS contract HHSN272201400008C and NIAID grant R01 AI117287. R.P.dV is a recipient of an ERC Starting Grant from the European Commission (802780) and a Beijerinck Premium of the Royal Dutch Academy of Sciences. Synthesis and microarray analysis were funded by a grant from the Netherlands Organization for Scientific Research (NWO TOPPUNT 718.015.003) to G.-J.B.

Publisher Copyright:
© 2021, The Author(s).

Funding

We would like to thank Andrew Duty and Tom Moran at the Department of Microbiology at the Icahn School of Medicine at Mount Sinai for letting us use their BLI device. We would also like to thank Edward Holmes at The University of Sidney for inspiring us to perform this study and for making the sequence information available. This work was partially funded by NIAID CEIRS contract HHSN272201400008C and NIAID grant R01 AI117287. R.P.dV is a recipient of an ERC Starting Grant from the European Commission (802780) and a Beijerinck Premium of the Royal Dutch Academy of Sciences. Synthesis and microarray analysis were funded by a grant from the Netherlands Organization for Scientific Research (NWO TOPPUNT 718.015.003) to G.-J.B.

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