biostudies-literatureUnknownSingh GNIAID NIH HHSNCI NIH HHSORFDO NIH HHSNovel influenza-like virus sequences previously identified in fish and amphibians were found to cluster as a sister clade of influenza B viruses, but have thus far remained uncharacterized. We demonstrate that salamander influenza-like virus (SILV) HA is functionally divergent from influenza B virus HA and does not bind to α 2,3- 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 at a wide range of pH conditions. SAEILV 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). Importantly, no cross-reactive antibodies against these HAs or NAs were found in the human serum, suggesting that humans are immunologically naïve to these viruses.bioRxiv : the preprint server for biology2025.05.08.652883https://www.ebi.ac.uk/biostudies/studies/S-EPMC12247948biostudies-literatureCharacterization of the glycoproteins of novel fish influenza B-like viruses.PMC1224794875N93021C0001475N93019C00051R01 AI16569275N91019C0005175N99019C00051Singh GBoons GJKrammer FBhavsar DHuang JSimon Vde Vries RPHan JFerguson JAWard AVasilev KfalseCharacterization of the glycoproteins of novel fish influenza B-like viruses.Novel influenza-like virus sequences previously identified in fish and amphibians were found to cluster as a sister clade of influenza B viruses, but have thus far remained uncharacterized. We demonstrate that salamander influenza-like virus (SILV) HA is functionally divergent from influenza B virus HA and does not bind to α 2,3- 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 at a wide range of pH conditions. SAEILV 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). Importantly, no cross-reactive antibodies against these HAs or NAs were found in the human serum, suggesting that humans are immunologically naïve to these viruses.2025-01-01T00:00:00Z2025 May2026-04-08T09:55:55.448Z2025-08-23T03:09:33.055ZS-EPMC122479484065480810.1101/2025.05.08.652883