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J. Virol. doi:10.1128/JVI.02296-07
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Cellular Proteasome Activity Facilitates Herpes Simplex Virus Entry at a Post-Penetration Step

Department of Microbiology and Immunology, Virginia Commonwealth University School of Medicine, Richmond, Virginia, 23298-0678

^* To whom correspondence should be addressed. Email: anicola{at}vcu.edu.

	Abstract

Herpes simplex virus (HSV) entry into cells is a multi-step process that engages the host cell machinery. The proteasome is a large, ATP-dependent, multi-subunit protease that plays a critical role in the maintenance of cell homeostasis. A battery of assays were used to demonstrate that proteasome inhibitors blocked an early step in HSV entry that occurred following capsid penetration into the cytosol but prior to capsid arrival at the nuclear periphery. Proteasome-dependent viral entry was not reliant on host or viral protein synthesis. MG132, a peptide aldehyde that competitively inhibits the degradative activity of the proteasome, had a reversible inhibitory effect on HSV entry. HSV can use endocytic or non-endocytic pathways to enter cells. These distinct entry routes were both dependent on proteasome-mediated proteolysis. In addition, HSV successfully entered cells in the absence of a functional host ubiquitin-activating enzyme, suggesting that viral entry is ubiquitin-independent. We propose that proteasomal degradation of virion and/or host proteins is required for efficient delivery of incoming HSV capsids to the nucleus.

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