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

• Published in: Nature communications 2021-10, Vol.12 (1), p.6161-6161, Article 6161
• Main Authors: Arunkumar, Guha Asthagiri, Bhavsar, Disha, Li, Tiehai, Strohmeier, Shirin, Chromikova, Veronika, Amanat, Fatima, Bunyatov, Mehman, Wilson, Patrick C., Ellebedy, Ali H., Boons, Geert-Jan, Simon, Viviana, de Vries, Robert P., Krammer, Florian
• Format: Article
• Language: English
• Subjects: 631/326/596/1578; 631/326/596/2116; 82/80; 82/83; Amino Acid Sequence; Amphibians; Animals; Antibodies, Monoclonal - immunology; Antibodies, Viral - immunology; Antigens; Cross Reactions; Exo-a-sialidase; Fish; Fishes - virology; Glycoproteins; Hemagglutinin Glycoproteins, Influenza Virus - chemistry; Hemagglutinin Glycoproteins, Influenza Virus - genetics; Hemagglutinin Glycoproteins, Influenza Virus - immunology; Hemagglutinin Glycoproteins, Influenza Virus - metabolism; Hemagglutinins; Humanities and Social Sciences; Humans; Influenza; Influenza B; Influenza B virus - classification; Influenza B virus - genetics; Influenza B virus - immunology; Influenza B virus - metabolism; Mastacembelus armatus; Mice; multidisciplinary; Neuraminidase - chemistry; Neuraminidase - genetics; Neuraminidase - immunology; Neuraminidase - metabolism; Orthomyxoviridae - classification; Orthomyxoviridae - genetics; Orthomyxoviridae - immunology; Orthomyxoviridae - metabolism; Phylogeny; Proteins; Receptors, Virus - metabolism; Science; Science (multidisciplinary); Seals; Viruses
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-26409-2

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. The recently identified Wuhan spiny eel influenza virus (WSEIV) sequence is more closely related to influenza B than A viruses. Here, the authors functionally characterize the putative surface glycoproteins of WSEIV and show that its NA-like protein has sialidase activity and its HA-like protein binds monosialic ganglioside 2.