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J. Virol. doi:10.1128/JVI.02330-07
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Venezuelan equine encephalitis virus capsid protein inhibits nuclear import in mammalian, but not in mosquito cells

Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555-1019; Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555-1072

^* To whom correspondence should be addressed. Email: elfrolov{at}UTMB.edu.

	Abstract

Venezuelan equine encephalitis virus (VEEV) represents a continuous public health threat in the US. It has the ability to cause fatal disease in humans, horses and other domestic animals. We recently demonstrated that replicating VEEV interferes with cellular transcription and uses this phenomenon as a means of downregulating a cellular antiviral response. VEEV capsid protein was found to play a critical role in this process, and its 35-aa-long peptide, fused with GFP, functioned as efficiently as did the entire capsid. We detected a significant fraction of VEEV capsid associated with nuclear envelope, which suggested that this protein might regulate nucleocytoplasmic trafficking. In this study, we demonstrate that VEEV capsid and its N-terminal sequence efficiently inhibit multiple receptor-mediated nuclear import pathways, but have no effect on passive diffusion of small proteins. The capsid protein of the Old World alphavirus, Sindbis virus (SINV), and the VEEV capsid having a previously defined frame-shift mutation were found to have no detectable effect on nuclear import. Importantly, the VEEV capsid did not noticeably interfere with nuclear import in the mosquito cells, and this might play a critical role in the ability of the virus to develop a persistent, life-long infection in mosquito vectors. These findings demonstrate a new aspect of VEEV-host cell interactions, and the results of this study are likely applicable to other New World alphaviruses, such as eastern and western equine encephalitis viruses.

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