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.