Arterivirus replicase processing : regulatory cascade or Gordian knot?
Aken, A.T. van
Citation
Aken, A. T. van. (2008, October 22). Arterivirus replicase processing : regulatory cascade or Gordian knot?. Retrieved from https://hdl.handle.net/1887/13216
Version: Corrected Publisher’s Version
License: Licence agreement concerning inclusion of doctoral thesis in the Institutional Repository of the University of Leiden
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Arterivirus replicase processing:
regulatory cascade or Gordian knot?
Proefschrift
ter verkrijging van
de graad van Doctor aan de Universiteit Leiden,
op gezag van de Rector Magnificus prof. mr. P.F. van der Heijden, volgens besluit van het College voor Promoties
te verdedigen op woensdag 22 oktober 2008 klokke 15.00 uur
door
Arnoldus Theodorus van Aken
geboren te Noordwijkerhout in 1972
Promotiecommissie
Promotores Prof. dr. E.J. Snijder Prof. dr. A.E. Gorbalenya (Moscow State University)
Referent Prof. dr. J. Ziebuhr
(The Queen’s University of Belfast)
Overige leden Prof. dr. R.C. Hoeben
Prof. dr. F. Koning
Prof. dr. W.J.M. Spaan
“ hardlopers zijn doodlopers”
Table of contents
Chapter 1 General introduction 7
Chapter 2 Chymotrypsin-like proteases as key regulators of the positive-sense RNA virus life cycle
21
Chapter 3 Expression, purification, and in vitro activity of an arterivirus main protease
59
Chapter 4 Structure of arterivirus nsp4: the smallest chymotrypsin-like protease with an Į/ȕ C-terminal extension and alternate conformations of the oxyanion hole
77
Chapter 5 Proteolytic activity and reverse genetics phenotype of EAV nsp4 protease mutants carrying replacements of residues Arg-4, Asp-119, and Arg-203
93
Chapter 6 Mutagenesis analysis of the nsp4 main protease reveals determinants of arterivirus replicase polyprotein autoprocessing
105
Chapter 7 Proteolytic maturation of replicase polyprotein pp1a by the nsp4 main protease is essential for equine arteritis virus replication and includes internal cleavage of nsp7
127
Chapter 8 General discussion 145
Summary 155 Samenvatting 159
Curriculum vitae 163
