The Hemagglutinin of Bat-Associated Influenza Viruses Is Activated by TMPRSS2 for pH-Dependent Entry into Bat but Not Human Cells

Hoffmann, Markus; Krüger, Nadine; Zmora, Pawel; Wrensch, Florian; Herrler, Georg; Pöhlmann, Stefan

BatFLUAV-HAL does not use sialic acids for host cell entry FLUAV employ alpha-2,3-(avian viruses) and alpha-2,6-linked (human viruses) sialic acids as receptors for host cell entry [47] [48] [49] [50] [51] . In order to assess the potential role of sialic acids in HALdriven entry, we pre-treated the cells with escalating doses of bacterial neuraminidase before transduction. Neuraminidase treatment of EpoNi/22.1 cells reduced transduction mediated by the FLUAV-HA proteins, as expected (Fig 4) . In contrast, sialidase treatment had no effect on pseudotype entry mediated by batFLUAV-HAL, NiV-F/G or VSV-G. Moreover, pre-treatment of EpoNi/22.1 cells at the highest dose (150 mU) even enhanced transduction driven by HAL and VSV-G (Fig 4) . These results indicate that HAL does not use sialic acids for host cell entry and suggest that removal of sialic acids might even increase batFLUAV infectivity, potentially by increasing accessibility of a cellular receptor.