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

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

doi:10.1038/s41467-021-26409-2

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.

Highlights

A panel of influenza virus-like sequences were recently documented in fish and amphibians
We address the antigenic conservation of the Wuhan spiny eel influenza virus (WSEIV) HA and NA using a panel of broadly cross-reactive monoclonal antibodies and a set of serum samples from humans positive for the influenza B virus
Along the lines of the whole virus genome alignments in the study identifying this virus, we observed the proximal clustering of the WSEIV HA and NA to influenza B virus HAs and NAs (Fig. 1A, E)

Summary

Introduction

A panel of influenza virus-like sequences were recently documented in fish and amphibians. We perform a functional and antigenic characterization of the glycoproteins of WSEIV to assess if it is a bona fide influenza virus potentially circulating in ray-finned fish. In addition to human infections, influenza A virus has been shown to have a broad host tropism, infecting a variety of different avian and mammalian species[2] This enhances the pandemic potential of these viruses due to an increased possibility of reassortment in a commonly infected host[3]. A study by Shi et al aimed at addressing this dearth of sampling in amphibians, fish, and reptiles, and identified 214 vertebrate species-associated virus sequences through a meta-transcriptomic approach Most of these viruses could be categorized into 17 vertebrate-specific viral families, significantly enhancing the diversity of viral families historically known to have mammalian or avian hosts. The surface viral glycoproteins, hemagglutinin (HA), and the neuraminidase (NA) of the WSEIV have a 45% and 48% amino acid identity to the respective HA and NA of influenza B viruses[9]

Methods

Results

Conclusion