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Journal of Virology, September 2009, p. 9304-9312, Vol. 83, No. 18
0022-538X/09/$08.00+0     doi:10.1128/JVI.01826-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Modification and Reorganization of the Cytoprotective Cellular Chaperone Hsp27 during Herpes Simplex Virus Type 1 Infection{triangledown}

Shomita S. Mathew, Megan P. Della Selva, and April D. Burch*

Wadsworth Center, The David Axelrod Institute, New York State Department of Health, Division of Infectious Diseases, 120 New Scotland Avenue, Albany, New York 12208

Received 29 August 2008/ Accepted 25 June 2009

Chaperone-enriched domains are formed in the nuclei of cells lytically infected with herpes simplex virus type 1 (HSV-1). These domains, called VICE, for virus induced chaperone enriched, contain Hsc70, Hsp70, Hsp40, Hsp90, polyubiquitinated proteins, and components of the proteasome machinery. Accumulating evidence indicates that these sites may be utilized during infection to sequester misfolded, modified, or otherwise unwanted proteins away from viral replication compartments, sites of robust transcription, DNA synthesis, and capsid maturation. To further explore the role of cellular chaperones and VICE domains during HSV-1 infection, we have analyzed the cytoprotective chaperone Hsp27. Here we present evidence that Hsp27, which is known to possess several antioxidant functions, is rapidly reorganized and modified at early stages in response to HSV-1 infection and signaling from the mitogen-activated protein kinase p38. Immunofluorescence analysis and fractionation experiments reveal disparate subcellular localizations of nonphosphorylated and phosphorylated forms of Hsp27 during wild-type HSV-1 infection. Unmodified forms of Hsp27 are localized in nuclear foci that are outside of replication compartments, adjacent to VICE domains, and in the cytoplasm. Conversely, we find that phosphorylated forms of Hsp27 are localized exclusively in the cytoplasm. Last, in cells depleted of all forms of Hsp27, virus replication is significantly reduced.


* Corresponding author. Mailing address: Wadsworth Center, The David Axelrod Institute, New York State Department of Health, Division of Infectious Diseases, 120 New Scotland Avenue, Albany, NY 12208. Phone: (518) 402-2233. Fax: (518) 402-4773. E-mail: aburch{at}wadsworth.org

{triangledown} Published ahead of print on 8 July 2009.


Journal of Virology, September 2009, p. 9304-9312, Vol. 83, No. 18
0022-538X/09/$08.00+0     doi:10.1128/JVI.01826-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.