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Journal of Virology, July 2007, p. 6785-6797, Vol. 81, No. 13
0022-538X/07/$08.00+0     doi:10.1128/JVI.00198-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Coxsackievirus B3 Proteins Directionally Complement Each Other To Downregulate Surface Major Histocompatibility Complex Class I

Christopher T. Cornell,^1, William B. Kiosses,² Stephanie Harkins,¹ and J. Lindsay Whitton^1*

Molecular and Integrative Neurosciences Department,¹ Core Microscopy Facility, The Scripps Research Institute, La Jolla, California²

Received 29 January 2007/ Accepted 3 April 2007

Picornaviruses carry a small number of proteins with diverse functions that subvert and exploit the host cell. We have previously shown that three coxsackievirus B3 (CVB3) proteins (2B, 2BC, and 3A) target the Golgi complex and inhibit protein transit. Here we investigate these effects in more detail and evaluate the distribution of major histocompatibility complex (MHC) class I molecules, which are critical mediators of the CD8⁺ T-cell response. We report that concomitant with viral protein synthesis, MHC class I surface expression is rapidly downregulated during infection. However, this phenomenon may not result solely from inhibition of anterograde trafficking; we propose a new mechanism whereby the CVB3 2B and 2BC proteins upregulate the internalization of MHC class I (and possibly other surface proteins), perhaps by focusing of endocytic vesicles at the Golgi complex. Thus, our findings indicate that CVB3 carries at least three nonstructural proteins that directionally complement one another; 3A disrupts the Golgi complex to inhibit anterograde transport, while 2B and/or 2BC upregulates endocytosis, rapidly removing proteins from the cell surface. Taken together, these effects may render CVB3-infected cells invisible to CD8⁺ T cells and untouchable by many antiviral effector molecules. This has important implications for immune evasion by CVB3.

Published ahead of print on 18 April 2007.

Present address: Biopharmaceutical Department, Allergan, Inc., 2525 Dupont Dr., Irvine, CA 92612.

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