Previous Article | Next Article 
Journal of Virology, August 2005, p. 10740-10749, Vol. 79, No. 16
0022-538X/05/$08.00+0 doi:10.1128/JVI.79.16.10740-10749.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.
Herpes Simplex Virus Type 1 DNA Polymerase Requires the Mammalian Chaperone Hsp90 for Proper Localization to the Nucleus
April D. Burch
and
Sandra K. Weller*
University of Connecticut Health Center, Department of Molecular, Microbial, and Structural Biology, MC3205, 263 Farmington Ave., Farmington, Connecticut 06030
Received 28 January 2005/
Accepted 21 April 2005
Many viruses and bacteriophage utilize chaperone systems for DNA replication and viral morphogenesis. We have previously shown that in the herpes simplex virus type 1 (HSV-1)-infected cell nucleus, foci enriched in the Hsp70/Hsp40 chaperone machinery are formed adjacent to viral replication compartments (A. D. Burch and S. K. Weller, J. Virol. 78:7175-7185, 2004). These foci have now been named virus-induced chaperone-enriched (VICE) foci. Since the Hsp90 chaperone machinery is known to engage the Hsp70/Hsp40 system in eukaryotes, the subcellular localization of Hsp90 in HSV-1-infected cells was analyzed. Hsp90 is found within viral replication compartments as well as in the Hsp70/Hsp40-enriched foci. Geldanamycin, an inhibitor of Hsp90, results in decreased HSV-1 yields and blocks viral DNA synthesis. Furthermore, we have found that the viral DNA polymerase is mislocalized to the cytoplasm in both infected and transfected cells in the presence of geldanamycin. Additionally, in the presence of an Hsp90 inhibitor, proteasome-dependent degradation of the viral polymerase was detected by Western blot analysis. These data identify the HSV-1 polymerase as a putative client protein of the Hsp90 chaperone system. Perturbations in this association appear to result in degradation, aberrant folding, and/or intracellular localization of the viral polymerase.
* Corresponding author. Mailing address: University of Connecticut Health Center, Department of Molecular, Microbial, and Structural Biology, MC3205, 263 Farmington Ave., Farmington, CT 06030. Phone: (860) 679-2310. Fax: (860) 679-1239. E-mail:
weller{at}nso2.uchc.edu.
Present address: The David Axelrod Institute, Wadsworth Center, NYSDOH, 120 New Scotland Ave., Albany, NY 12201-2002.
Journal of Virology, August 2005, p. 10740-10749, Vol. 79, No. 16
0022-538X/05/$08.00+0 doi:10.1128/JVI.79.16.10740-10749.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.
This article has been cited by other articles:
-
Mathew, S. S., Della Selva, M. P., Burch, A. D.
(2009). Modification and Reorganization of the Cytoprotective Cellular Chaperone Hsp27 during Herpes Simplex Virus Type 1 Infection. J. Virol.
83: 9304-9312
[Abstract]
[Full Text]
-
Liu, Z., Yang, F., Robotham, J. M., Tang, H.
(2009). Critical Role of Cyclophilin A and Its Prolyl-Peptidyl Isomerase Activity in the Structure and Function of the Hepatitis C Virus Replication Complex. J. Virol.
83: 6554-6565
[Abstract]
[Full Text]
-
Livingston, C. M., DeLuca, N. A., Wilkinson, D. E., Weller, S. K.
(2008). Oligomerization of ICP4 and Rearrangement of Heat Shock Proteins May Be Important for Herpes Simplex Virus Type 1 Prereplicative Site Formation. J. Virol.
82: 6324-6336
[Abstract]
[Full Text]
-
Taguwa, S., Okamoto, T., Abe, T., Mori, Y., Suzuki, T., Moriishi, K., Matsuura, Y.
(2008). Human Butyrate-Induced Transcript 1 Interacts with Hepatitis C Virus NS5A and Regulates Viral Replication. J. Virol.
82: 2631-2641
[Abstract]
[Full Text]
-
Cheng, X., Belshan, M., Ratner, L.
(2008). Hsp40 Facilitates Nuclear Import of the Human Immunodeficiency Virus Type 2 Vpx-Mediated Preintegration Complex. J. Virol.
82: 1229-1237
[Abstract]
[Full Text]
-
Kyratsous, C. A., Silverstein, S. J.
(2007). BAG3, a Host Cochaperone, Facilitates Varicella-Zoster Virus Replication. J. Virol.
81: 7491-7503
[Abstract]
[Full Text]
-
Geller, R., Vignuzzi, M., Andino, R., Frydman, J.
(2007). Evolutionary constraints on chaperone-mediated folding provide an antiviral approach refractory to development of drug resistance. Genes Dev.
21: 195-205
[Abstract]
[Full Text]
-
Wilkinson, D. E., Weller, S. K.
(2006). Herpes simplex virus type I disrupts the ATR-dependent DNA-damage response during lytic infection. J. Cell Sci.
119: 2695-2703
[Abstract]
[Full Text]