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

Host Cell Entry by Bat-Associated Influenza Viruses limited information is available, which indicate that batFLUAV do not engage with canonical FLUAV receptors [17, [22] [23] [24] . However, until very recently no proof of functional activity of batFLUAV surface proteins was available [17, [22] [23] [24] [25] [26] [27] . Here, we employed a vector system to analyze batFLUAV-HAL and -NAL. We show that HAL mediates entry into certain bat cell lines and that entry does not depend on the presence of sialic acids on the cell surface. Moreover, we demonstrate that NAL is not required for production of infectious HAL-bearing particles, at least under the conditions examined. Finally, our studies revealed that trypsin and TTSPs activate HAL for host cell entry.