Abstract
ABSTRACT The ability of the 3A protein of coxsackievirus B (CVB) to inhibit protein secretion was investigated for this study. Here we show that the ectopic expression of CVB 3A blocked the transport of both the glycoprotein of vesicular stomatitis virus, a membrane-bound secretory marker, and the alpha-1 protease inhibitor, a luminal secretory protein, at a step between the endoplasmic reticulum (ER) and the Golgi complex. CVB 3A contains a conserved proline-rich region in its N terminus. The importance of this proline-rich region was investigated by introducing Pro-to-Ala substitutions. The mutation of Pro 19 completely abolished the ability of 3A to inhibit ER-to-Golgi transport. The mutation of Pro 14 , Pro 17 , or Pro 20 also impaired this ability, but to a lesser extent. The mutation of Pro 18 had no effect. We also investigated the possible importance of this proline-rich region for the function of 3A in viral RNA replication. To this end, we introduced the Pro-to-Ala mutations into an infectious cDNA clone of CVB3. The transfection of cells with in vitro-transcribed RNAs of these clones gave rise to mutant viruses that replicated with wild-type characteristics. We concluded that the proline-rich region in CVB 3A is required for its ability to inhibit ER-to-Golgi transport, but not for its function in viral RNA replication. The functional relevance of the proline-rich region is discussed in light of the proposed structural model of 3A.
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Dates
Type | When |
---|---|
Created | 20 years, 5 months ago (March 28, 2005, 1:47 p.m.) |
Deposited | 3 years, 6 months ago (March 5, 2022, 5:06 a.m.) |
Indexed | 1 week, 1 day ago (Aug. 29, 2025, 6:10 a.m.) |
Issued | 20 years, 4 months ago (April 15, 2005) |
Published | 20 years, 4 months ago (April 15, 2005) |
Published Print | 20 years, 4 months ago (April 15, 2005) |
@article{Wessels_2005, title={A Proline-Rich Region in the Coxsackievirus 3A Protein Is Required for the Protein To Inhibit Endoplasmic Reticulum-to-Golgi Transport}, volume={79}, ISSN={1098-5514}, url={http://dx.doi.org/10.1128/jvi.79.8.5163-5173.2005}, DOI={10.1128/jvi.79.8.5163-5173.2005}, number={8}, journal={Journal of Virology}, publisher={American Society for Microbiology}, author={Wessels, Els and Duijsings, Daniël and Notebaart, Richard A. and Melchers, Willem J. G. and van Kuppeveld, Frank J. M.}, year={2005}, month=apr, pages={5163–5173} }