Expression of 9-O- and 7,9-O-acetyl modified sialic acid in cells and their effects on influenza viruses

Karen N. Barnard; Brian R. Wasik; Justin R. LaClair; Wendy S. Weichert; Brynn K. Lawrence; Colin R. Parrish

One candidate for control of these modifications is SIAE. When we knocked 319 SIAE out of HEK-293 and A549 cells, we saw an increase in 9-O-Ac that was still 320 The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. . https://doi.org/10.1101/650341 doi: bioRxiv preprint This is unsurprising, as >95% of the Sia is un-acetylated Neu5Ac which can be utilized 340 by IAV as a receptor for binding and entry. However, the 1-2% of 9-O-Ac on the surface 341 of WT MDCK-NBL2 cells was sufficient for ICV virus binding and entry, and that cell 342 susceptibility was lost when CasD1 was inactivated. Similar results are likely seen for 343 other viruses that use these modified Sia as a receptor, including human coronaviruses 344 OC43 and HKU1 (42). present at levels too low to affect IAV, they are expressed at much higher levels in 357 mucosal tissues and in secreted mucins of many animals and tissues, which may 358 provide a more effective barrier (10, 11, 43-45). In future work we are examining these 359 processes for mucus and other sources in different animals. 360