Role of Glycoconjugates and Mammalian Sialidases Involved in Viral Infection and Neural Function

Abstract

Glycoconjugates are present in various organisms, ranging from animals to viruses. Glycoconjugates are involved in several biologically significant functions, including viral infection and neurotransmission. However, the role of glycoconjugates in virus replication and neural function remains unknown. We discovered that the influenza A virus (IAV) binds to sulfatide, which lacks a sialic acid residue, and that delivering sulfatide combined with newly synthesized IAV hemagglutinin (HA) to the target plasma membrane induces the translocation of viral ribonucleoprotein complexes from the nucleus to the cytoplasm. Molecular species of sialic acid are largely classified as N-acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc). We discovered that two amino acids in IAV H3 HA play a critical role in the recognition of Neu5Ac and Neu5Gc. Also, we observed that human parainfluenza virus types 1 (hPIV-1) and 3 (hPIV-3) bind to different forms of gangliosides. These viruses preferentially recognized oligosaccharides containing branched N-acetyllactosaminoglycans with terminal Neu5Acα2-3Gal. Neu5Gcα2-3Gal- and NeuAcα2-6Gal-containing receptors were identified by hPIV-3, but not by hPIV-1. We constructed a novel sialidase fluorescent substrate, 2-benzothiazol-2-yl-phenol derivative-based N-acetylneuraminic acid (BTP3-Neu5Ac), which detects sialidase activity in living mammalian tissues and virus-infected cells expressing viral neuraminidase. We discovered that neural activity-dependent desialylation by sialidase contributes to rat hippocampal memory processing. Using BTP3-Neu5Ac, we developed a rapid and sensitive approach for detecting and isolating drug-resistant influenza viruses. This review summarizes the role of sialylglycoconjugates and sulfatide in virus replication as well as mammalian sialidases involved in neural function and insulin secretion.