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Meiling Dai

Friday 22 September 2017

Tuning of influenza A virus neuraminidase activity

Promotor: prof.dr. F.J.M. (Frank) van Kuppeveld
Supervisor: dr. C.A.M. (Xander) de Haan
Date: 22 September 2017
Time: 12.45 h

Summary
Influenza A virus (IAV) infections constantly pose great threats to public health and cause large economic burdens. There are two important glycoproteins in the IAV virus membrane, hemagglutinin (HA) and neuraminidase (NA), both of which recognize sialic acids (SIAs). Initiation of virus infection involves binding of multiple HAs to SIAs on carbohydrate side chains of cell surface glycoproteins and glycolipids. As the second most abundant viral glycoprotein, NA is a receptor-destroying enzyme that removes SIAs from infected cell surfaces upon virus replication so that newly synthesized viruses are released from these cells and can infect new cells. The sialidase activity also prevents aggregation of newly synthesized virions by removing SIAs from their own glycoproteins.

Despite the important role of NA in virus infection, replication and transmission, it appears that this protein is relatively understudied compared to its HA counterpart. While HA receptor-binding avidity and specificity have been studied in detail, much less is known about the molecular determinants that mediate the specificity and activity of IAV NA proteins. The overall aim of this thesis was to unravel to what extent and how IAV NA protein activity is modulated during virus evolution. The preceding chapters of this thesis described our investigations in the NA functionality, mainly enzymatic activity, by using a recombinant soluble protein approach. The main findings are summarized and discussed in a broader perspective, which is divided over three main topics involving 1) investigation of NA enzyme activity and substrate specificity, 2) mechanisms of tuning IAV NA activity, and 3) HA/NA balance and virus evolution.

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