We have shown that the host chaperone molecules are redirected during Herpes Simplex Virus Type-1 (HSV-1) infection. In the HSV-1-infected cell, we found the cellular chaperone machinery (Hsp90, Hsp70 and Hsp40) is localized at virus-specific sites and may be in an activated' state similar to that found in tumor tissues. This activated chaperone complex is the known target of Hsp90- inhibitor molecules. Preliminary studies suggest that inhibitors of Hsp90 block HSV-1 infection very early in infection, prior to DNA synthesis. This proposal describes experiments to test the hypothesis that in the virus-infected cell, the chaperone machinery is in an activated state similar to that found in tumor tissues and that this complex represents a novel antiviral target.
Specific Aim 1 will identify the viral proteins that interact with Hsp90 using a proteomic approach including 2D-gel electrophoresis and tandem mass spectroscopy.
Specific Aim 2 will test the hypothesis that Hsp90 is required for efficient HSV-1 DNA replication by isolating resistance mutants to Hsp90-inhibitors. The studies described herein will not only provide information about the basic biology of chaperone-directed processes occurring in the HSV-1-infected cell, but also impart knowledge about the new frontier of antiviral chemotherapeutics that target the host-pathogen interface. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Career Transition Award (K22)
Project #
1K22AI062991-01
Application #
6852023
Study Section
Microbiology and Infectious Diseases B Subcommittee (MID)
Program Officer
Beisel, Christopher E
Project Start
2005-12-15
Project End
2007-11-30
Budget Start
2005-12-15
Budget End
2006-11-30
Support Year
1
Fiscal Year
2006
Total Cost
$162,000
Indirect Cost
Name
Wadsworth Center
Department
Type
DUNS #
153695478
City
Menands
State
NY
Country
United States
Zip Code
12204
Mathew, Shomita S; Bryant, Patrick W; Burch, April D (2010) Accumulation of oxidized proteins in Herpesvirus infected cells. Free Radic Biol Med 49:383-91
Mathew, Shomita S; Della Selva, Megan P; Burch, April D (2009) Modification and reorganization of the cytoprotective cellular chaperone Hsp27 during herpes simplex virus type 1 infection. J Virol 83:9304-12