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Journal of Virology, October 2006, p. 9865-9875, Vol. 80, No. 19
0022-538X/06/$08.00+0     doi:10.1128/JVI.00561-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Role of RNA Structure and RNA Binding Activity of Foot-and-Mouth Disease Virus 3C Protein in VPg Uridylylation and Virus Replication

Arabinda Nayak,^1, Ian G. Goodfellow,² Kathryn E. Woolaway,^1, James Birtley,³ Stephen Curry,³ and Graham J. Belsham^1*

BBSRC Institute for Animal Health, Pirbright, Woking, Surrey GU24 0NF, United Kingdom,¹ Department of Virology, Faculty of Medicine, Imperial College, St Mary's Campus, London W2 1PG, United Kingdom,² Biophysics Section, Blackett Laboratory, Imperial College, South Kensington Campus, London SW7 2AZ, United Kingdom³

Received 17 March 2006/ Accepted 7 July 2006

The uridylylation of the VPg peptide primer is the first stage in the replication of picornavirus RNA. This process can be achieved in vitro using purified components, including 3B (VPg) with the RNA dependent RNA polymerase (3D^pol), the precursor 3CD, and an RNA template containing the cre/bus. We show that certain RNA sequences within the foot-and-mouth disease virus (FMDV) 5' untranslated region but outside of the cre/bus can enhance VPg uridylylation activity. Furthermore, we have shown that the FMDV 3C protein alone can substitute for 3CD, albeit less efficiently. In addition, the VPg precursors, 3B₃3C and 3B₁₂₃3C, can function as substrates for uridylylation in the absence of added 3C or 3CD. Residues within the FMDV 3C protein involved in interaction with the cre/bus RNA have been identified and are located on the face of the protein opposite from the catalytic site. These residues within 3C are also essential for VPg uridylylation activity and efficient virus replication.

Present address: Department of Microbiology and Immunology, University of California, San Francisco, CA 94143-2280.

Present address: Department of Medical Genetics and Microbiology, University of Toronto, Toronto, Ontario, Canada M5G 1A8.

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