Post-Glycosylation Modification of Sialic Acid and Its Role in Virus Pathogenesis

Abstract

Sialic acids are a family of nine carbon keto-aldononulosonic acids presented at the terminal ends of glycans on cellular membranes. α-Linked sialoglycoconjugates often undergo post-glycosylation modifications, among which O-acetylation of N-acetyl neuraminic acid (Neu5Ac) is the most common in mammalian cells. Isoforms of sialic acid are critical determinants of virus pathogenesis. To date, the focus of viral receptor-mediated attachment has been on Neu5Ac. O-Acetylated Neu5Acs have been largely ignored as receptor determinants of virus pathogenesis, although it is ubiquitous across species. Significantly, the array of structures resulting from site-specific O-acetylation by sialic acid O-acetyltransferases (SOATs) provides a means to examine specificity of viral binding to host cells. Specifically, C 4 O-acetylated Neu5Ac can influence virus pathogenicity. However, the biological implications of only O-acetylated Neu5Ac at C 7-9 have been explored extensively. This review will highlight the biological significance, extraction methods, and synthetic modifications of C 4 O-acetylated Neu5Ac that may provide value in therapeutic developments and targets to prevent virus related diseases.Abstract: Sialic acids are a family of nine carbon keto-aldononulosonic acids presented at the terminal ends of glycans on cellular membranes. α-Linked sialoglycoconjugates often undergo postglycosylation modifications, among which O-acetylation of N-acetyl neuraminic acid (Neu5Ac) is the most common in mammalian cells. Isoforms of sialic acid are critical determinants of virus pathogenesis. To date, the focus of viral receptor-mediated attachment has been on Neu5Ac. O-Acetylated Neu5Acs have been largely ignored as receptor determinants of virus pathogenesis, although it is ubiquitous across species. Significantly, the array of structures resulting from sitespecific O-acetylation by sialic acid O-acetyltransferases (SOATs) provides a means to examine specificity of viral binding to host cells. Specifically, C4 O-acetylated Neu5Ac can influence virus pathogenicity. However, the biological implications of only O-acetylated Neu5Ac at C7-9 have been explored extensively. This review will highlight the biological significance, extraction methods, and synthetic modifications of C4 O-acetylated Neu5Ac that may provide value in therapeutic developments and targets to prevent virus related diseases.

Correlation of serum N-Acetylneuraminic acid with the risk and prognosis of acute coronary syndrome: a prospective cohort study

“…Recently, Neu5Ac has been proposed to have multiple biological functions. As a viral receptor, it is closely related to malignant transformation, cancer metastasis, invasion, loss of contact inhibition, cell adhesion reduction and antigenicity [31][32][33]. However, the mechanism of its role in CAD has not been fully understood.…”

Integrative Network Analysis of Predicted miRNA-Targets Regulating Expression of Immune Response Genes in Bovine Coronavirus Infection

“…The gene NANS, which codes for N-acetyl-9-0-acetylneuraminic acid (van Karnebeek et al, 2016), was included in our study due to its particular involvement in BCoV, despite not satisfying all the stipulations. This sialic acid has been determined to be the receptor onto which the S protein of BCoV binds (Schultze and Herrler, 1993;Belouzard et al, 2012;Park, 2019). Interestingly, NANS is not involved in immune response unlike the remainder of the examined genes.…”

SARS-CoV-2 Evolutionary Adaptation toward Host Entry and Recognition of Receptor O-Acetyl Sialylation in Virus–Host Interaction

“…De-acetylation reagents such as NaOH or NaIO 4 treatment completely hemagglutinate Neu4,5Ac2 by elimination of the C4- O -acetyl group [ 33 ]. The C4- O -acetyl Neu5Ac species are found in various sources such as equine erythrocyte GM3, starfish A. rubens and fish [ 34 , 35 , 36 , 37 , 38 ]. C4- O -acetylated Neu5Ac facilitates the initial attachment of viruses to target cells.…”

“…C4- O -Ac Neu5Ac is the major receptor determinant of ISAV in receptor binding and destruction [ 38 ], while the influenza C virus recognizes C9- O -Ac Neu5Ac. The acetylesterase RDE of ISAV cleaves C4- O -Ac via 4-SA- O -acetylesterase with a short turnover time, whereas C9- O -Ac Neu5Ac is cleaved by 9-SA- O -acetylesterase with a long turnover time [ 34 ].…”