Expression of 9-O- and 7,9-O-Acetyl Modified Sialic Acid in Cells and Their Effects on Influenza Viruses

Barnard, Karen N.; Wasik, Brian R.; LaClair, Justin R.; Buchholz, David W.; Weichert, Wendy S.; Alford-Lawrence, Brynn K.; Aguilar, Hector C.; Parrish, Colin R.

In summary, we have shown that these modifications are present in different cell lines sourced from different species of animals, but they make up a small minority of the total Sia present. In addition, these modifications vary considerably in their localization and have an inherent heterogeneity within cell populations. While the presence of both 7,9-O-and 9-O-Ac were dependent on the activity of CasD1, the relative proportions, levels of expression, and localization appear to be controlled by more complex mechanisms than simply the expression of CasD1 and SIAE. How this regulated expression affects cell homeostasis is unknown, but it is likely relevant during development, immune responses, and in cancers that show dysregulation of 7,9-O-and 9-O-Ac expression. For viruses such as ICV and IDV that rely on 9-O-Ac for infection, the low levels seen on cell surfaces are sufficient for infection. We found that 7,9-O-and 9-O-Ac do have inhibitory activity on HA binding and NA cleavage when present at higher levels. Although these modifications are present on cell surfaces at levels too low to affect IAV and IBV infection, they are expressed at much higher levels in mucosal tissues and in secreted mucus proteins of many animals, which may provide a more effective barrier (10, 11, (51) (52) (53) . We are currently examining these processes for secreted mucus and other sources in different animals.