The Specificity of Viral Sialidases

1 The action of sialidases from Newcastle disease virus (NDV), influenzaA 2 virus (IA2V) and fowl plague virus (FPV) on sialyloligosaccharide substrates containing α2 ‐ 3, α2 ‐ 6 or α2 ‐ 8 linkages was studied. 2 In all cases 2‐ 3‐linked sialic acids were preferentially released. Compared with II 6 Neu5AcLac, all 2–6‐ linked substrates, including sialyl‐ N ‐acetyllactosamine and its asparaginyl derivative, a urinary hexasaccharide and Neu5Ac(2–6)GalNAc were cleaved at improved rates by NDV and less by FPV sialidases. In the case of IA 2 V sialidase the asparaginyl oligosaccharide was very poorly cleaved, illustrating a variation in viral strain specificity. 3 A decrease in relative rates was observed in the order NDV >IA 2 V > FPV for substrates with 2–3 linkages relative to II6Neu5AcLac. The greatest relative rate was 470‐fold higher. The 2–3‐linked sialyl‐ N ‐acetyl‐lactosaminylasparagine and IV 3 Neu5AcLcOse 4 were poor substrates for the IA 2 V sialidase, but the rates were greater than with the 2–6‐linked substrates. 4 The ganglioside substrate II 3 Neu5AcLacCer showed lower activity than its oligosaccharide analogue, but neither II 3 Neu5AcGgOse 4 Cer nor its oligosaccharide were substrates. 5 The Km values for 2–6‐linked substrates were generally of the order 10 mM while those for the 2–3‐ linked substrates were approximately 1 mM. The V values were consistently higher for the 2–3‐linked substrates. IV 3 Neu5AcLcOse 4 showed high Km and very high V values, while the 2–8‐linked disialyllactose showed this trend only with NDV enzyme, the IA 2 V and FPV sialidases exhibiting high Km and low V values. 6 The results are discussed in the light of the current knowledge of viral sialidase specificity and relative to the binding of virus particles to cell surfaces.