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.

At least one sialate O-acetylesterase (SIAE) enzyme regulates the display of 7,9-Oand 9-O-Ac in many cells and tissues (Fig. 1B) . The SIAE gene encodes two isoforms that vary in the presence of a proposed C-terminal localization tag in the lysosomal form (Lse) that is absent from the cytosolic form (Cse) (12) . However, the processes that regulate the expression and activity of these two isoforms remain poorly defined. Lse has been found to localize to the Golgi compartment and/or endoplasmic reticulum (ER) and on the surfaces of cells when overexpressed, with the majority being secreted into the supernatant (12) . Antibody staining shows that Cse is found diffusely throughout the cytosol, where it is thought to remove 9-O-and 7-O-acetyl groups to recycle the Sia for reuse in glycosylation (12) . Despite the reports of distinct protein expression in mouse tissues, bioinformatic analysis of RNA expression in human cells and tissues show mRNA corresponding to the Lse form of SIAE and none responding to the Cse form (13) . It is therefore still unclear how these two isoforms are regulated in humans or other animals, whether their expression relates to CasD1, or what controls the levels and locations of 9-O-and 7,9-O-Ac expression.