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J. Virol. doi:10.1128/JVI.00393-06
Copyright (c) 2006, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Inhibition of the secretory pathway by the Foot-and-Mouth Disease Virus 2BC protein is reproduced by co-expression of 2B with 2C and the site of inhibition is determined by the subcellular location of 2C

Institute for Animal Health, Pirbright Laboratory, Ash Road, Pirbright, Surrey GU24 0NF, UK; University of St Andrews, School of Biology, Centre for Biomolecular Sciences, North Haugh, St Andrews KY16 9ST, UK

^* To whom correspondence should be addressed. Email: t.wileman{at}uea.ac.uk.

	Abstract

Infection of cells with picornaviruses can lead to a block in protein secretion. For poliovirus (PV) this is achieved by the 3A protein, and the consequent reduction in secretion of proinflammatory cytokines and surface expression of MHC class 1 proteins may inhibit host immune responses ‘in vivo'. Foot-and-mouth disease virus (FMDV), another picornavirus, can cause persistent infection of ruminants suggesting it too may inhibit immune responses. Endoplasmic reticulum (ER)-to-Golgi transport of proteins is blocked by the FMDV 2BC protein. The observation that 2BC is processed to 2B and 2C during infection, and that individual 2B and 2C proteins are unable to block secretion, stimulated us to study the effects of 2BC processing on the secretory pathway. Even though 2BC was processed rapidly to 2B and 2C, protein transport to the plasma membrane was still blocked in FMDV infected cells. The block could be reconstituted by co-expression of 2B and 2C, showing that processing of 2BC did not compromise the ability of FMDV to slow secretion. Under these conditions 2C was located to the Golgi and the block in transport also occurred in the Golgi. Interestingly, the block in transport could be redirected to the ER when 2B was co-expressed with a 2C protein fused to an ER retention element. Thus, for FMDV a block in secretion is dependent on both 2B and 2C, with the latter determining the site of the block.

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