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.

Sia O-acetylation and deacetylation play important roles in many different biological processes, particularly in development, cancer, and immunology. For example, O-acetyl modifications to Sia may alter the binding of host lectins, including siglecs (3, 5, 14) . Siglecs are regulators of many different cell functions and developmental processes; examples include B-and T cells, where the presence of 9-O-acetyl Sia modulates immune cell activation and differentiation (15) . In B cells, negative regulation of B-cell receptor (BCR) activation by siglec CD22 is mediated by binding to Neu5Ac-terminated glycan chains on the BCR, which can be blocked by O-acetyl modifications (16, 17) . The presence of 9-O-Ac can also reduce the activity of sialidases, including human neuraminidases (18) . Incorrect regulation of 9-O-Ac, 7,9-O-Ac, and SIAE activity has been linked to autoimmune disorders through the development of autoantibodies (17, 19) . 9-O-Ac and 7,9-O-Ac, and their regulation by SIAE also appear to play important roles during early stages of embryonic development, spermatogenesis, and in different forms of cancer, including acute lymphoblastic leukemia, colon cancer, and breast cancer (20) (21) (22) (23) .