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.

Common chemical additions include O-acetyl modifications to the C-4, -7, -8, and/or -9 positions, resulting in a variety of combinations, including Neu4,5Ac, Neu5,9Ac 2 , and Neu5,7,9Ac 3 Sia. The addition of O-acetyl modifications (O-Ac) to the C-7 and/or C-9 positions is mediated by the sialate O-acetyltransferase enzyme, Cas1 domain containing 1 (CasD1) (Fig. 1B ). CasD1 appears to add acetyl groups to the C-7 position of Sia, from which it may migrate to the C-8 and C-9 position under physiological conditions, allowing the possible addition of another acetyl group to C-7 (6, 7) . A migrase enzyme has been proposed to aid in the transfer of the acetyl group from C-7 to C-9; however, a specific enzyme has yet to be identified (5, 8, 9) . CasD1 is localized in the late Golgi compartment, so acetyl modifications are added during the later stages of protein glycosylation. The regulatory processes that control the number of acetyl groups added or their positions have not been well defined, although clear differences in expression of 7,9-O-Ac and 9-O-Ac have been reported in mouse and human cells and tissues, in chicken embryos, and in the tissues of some other animals (10, 11) . CasD1 uses acetyl coenzyme A and likely has a preference for CMP-Neu5Ac as a substrate so that it is less active on CMP-Neu5Gc (7) .