This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Mohr, I.
Right arrow Articles by Gluzman, Y.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mohr, I.
Right arrow Articles by Gluzman, Y.

 Previous Article  |  Next Article 

Journal of Virology, June 2001, p. 5189-5196, Vol. 75, No. 11
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.11.5189-5196.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

A Herpes Simplex Virus Type 1 gamma 34.5 Second-Site Suppressor Mutant That Exhibits Enhanced Growth in Cultured Glioblastoma Cells Is Severely Attenuated in Animals

Ian Mohr,1,* David Sternberg,1 Stephen Ward,2 David Leib,2 Matthew Mulvey,1 and Yakov Gluzman3,dagger

Department of Microbiology and Kaplan Comprehensive Cancer Center, New York University School of Medicine, New York, New York 100161; Department of Ophthalmology, Washington University School of Medicine, St. Louis, Missouri 631102; and Lederle Laboratories, Wyeth-Ayerst Research, Pearl River, New York 109653

Received 10 October 2000/Accepted 27 February 2001

We describe here the neurovirulence properties of a herpes simplex virus type 1 gamma 34.5 second-site suppressor mutant. gamma 34.5 mutants are nonneurovirulent in animals and fail to grow in a variety of cultured cells due to a block at the level of protein synthesis. Extragenic suppressors with restored capacity to replicate in cells that normally do not support the growth of the parental gamma 34.5 deletion mutant have been isolated. Although the suppressor virus reacquires the ability to grow in nonpermissive cultured cells, it remains severely attenuated in mice and is indistinguishable from the mutant gamma 34.5 parent virus at the doses investigated. Repairing the gamma 34.5 mutation in the suppressor mutant restores neurovirulence to wild-type levels. These studies illustrate that (i) the protein synthesis and neurovirulence defects observed in gamma 34.5 mutant viruses can be genetically separated by an extragenic mutation at another site in the viral chromosome; (ii) the extragenic suppressor mutation does not affect neurovirulence; and (iii) the attenuated gamma 34.5 mutant, which replicates poorly in many cell types, can be modified by genetic selection to generate a nonpathogenic variant that regains the ability to grow robustly in a nonpermissive glioblastoma cell line. As this gamma 34.5 second-site suppressor variant is attenuated and replicates vigorously in neoplastic cells, it may have potential as a replication-competent, viral antitumor agent.

* Corresponding author. Mailing address: Department of Microbiology, New York University School of Medicine, 550 First Ave., New York, NY 10016. Phone: (212) 263-0415. Fax: (212) 263-8276. E-mail: ian.mohr{at}med.nyu.edu.

dagger Deceased.

Journal of Virology, June 2001, p. 5189-5196, Vol. 75, No. 11
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.11.5189-5196.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Jin, H., Ma, Y., Prabhakar, B. S., Feng, Z., Valyi-Nagy, T., Yan, Z., Verpooten, D., Zhang, C., Cao, Y., He, B. (2009). The {gamma}134.5 Protein of Herpes Simplex Virus 1 Is Required To Interfere with Dendritic Cell Maturation during Productive Infection. J. Virol. 83: 4984-4994 [Abstract] [Full Text]  
  • Verpooten, D., Ma, Y., Hou, S., Yan, Z., He, B. (2009). Control of TANK-binding Kinase 1-mediated Signaling by the {gamma}134.5 Protein of Herpes Simplex Virus 1. J. Biol. Chem. 284: 1097-1105 [Abstract] [Full Text]  
  • Sanchez, R., Mohr, I. (2007). Inhibition of Cellular 2'-5' Oligoadenylate Synthetase by the Herpes Simplex Virus Type 1 Us11 Protein. J. Virol. 81: 3455-3464 [Abstract] [Full Text]  
  • Mulvey, M., Arias, C., Mohr, I. (2007). Maintenance of Endoplasmic Reticulum (ER) Homeostasis in Herpes Simplex Virus Type 1-Infected Cells through the Association of a Viral Glycoprotein with PERK, a Cellular ER Stress Sensor. J. Virol. 81: 3377-3390 [Abstract] [Full Text]  
  • Campbell, S. A., Mulvey, M., Mohr, I., Gromeier, M. (2007). Attenuation of Herpes Simplex Virus Neurovirulence with Picornavirus cis-Acting Genetic Elements. J. Virol. 81: 791-799 [Abstract] [Full Text]  
  • Hu, J. C., Booth, M. J., Tripuraneni, G., Davies, D., Zaidi, S. A.A., Tamburo de Bella, M., Slade, M. J., Marley, S. B., Gordon, M. Y.A., Coffin, R. S., Coombes, R. C., Kamalati, T. (2006). A Novel HSV-1 Virus, JS1/34.5-/47-, Purges Contaminating Breast Cancer Cells From Bone Marrow.. Clin. Cancer Res. 12: 6853-6862 [Abstract] [Full Text]  
  • Shah, A. C., Price, K. H., Parker, J. N., Samuel, S. L., Meleth, S., Cassady, K. A., Yancey Gillespie, G., Whitley, R. J., Markert, J. M. (2006). Serial Passage through Human Glioma Xenografts Selects for a {Delta}{gamma}134.5 Herpes Simplex Virus Type 1 Mutant That Exhibits Decreased Neurotoxicity and Prolongs Survival of Mice with Experimental Brain Tumors.. J. Virol. 80: 7308-7315 [Abstract] [Full Text]  
  • Mulvey, M., Camarena, V., Mohr, I. (2004). Full Resistance of Herpes Simplex Virus Type 1-Infected Primary Human Cells to Alpha Interferon Requires both the Us11 and {gamma}134.5 Gene Products. J. Virol. 78: 10193-10196 [Abstract] [Full Text]  
  • Jing, X., Cerveny, M., Yang, K., He, B. (2004). Replication of Herpes Simplex Virus 1 Depends on the {gamma}134.5 Functions That Facilitate Virus Response to Interferon and Egress in the Different Stages of Productive Infection. J. Virol. 78: 7653-7666 [Abstract] [Full Text]  
  • Mulvey, M., Poppers, J., Sternberg, D., Mohr, I. (2003). Regulation of eIF2{alpha} Phosphorylation by Different Functions That Act during Discrete Phases in the Herpes Simplex Virus Type 1 Life Cycle. J. Virol. 77: 10917-10928 [Abstract] [Full Text]  
  • Cheng, G., Yang, K., He, B. (2003). Dephosphorylation of eIF-2{alpha} Mediated by the {gamma}134.5 Protein of Herpes Simplex Virus Type 1 Is Required for Viral Response to Interferon but Is Not Sufficient for Efficient Viral Replication. J. Virol. 77: 10154-10161 [Abstract] [Full Text]  
  • Ward, S. L., Scheuner, D., Poppers, J., Kaufman, R. J., Mohr, I., Leib, D. A. (2003). In Vivo Replication of an ICP34.5 Second-Site Suppressor Mutant following Corneal Infection Correlates with In Vitro Regulation of eIF2{alpha} Phosphorylation. J. Virol. 77: 4626-4634 [Abstract] [Full Text]  
  • Cheng, G., Brett, M.-E., He, B. (2002). Signals That Dictate Nuclear, Nucleolar, and Cytoplasmic Shuttling of the {gamma}134.5 Protein of Herpes Simplex Virus Type 1. J. Virol. 76: 9434-9445 [Abstract] [Full Text]  
  • Child, S. J., Jarrahian, S., Harper, V. M., Geballe, A. P. (2002). Complementation of Vaccinia Virus Lacking the Double-Stranded RNA-Binding Protein Gene E3L by Human Cytomegalovirus. J. Virol. 76: 4912-4918 [Abstract] [Full Text]  
  • Mao, H., Rosenthal, K. S. (2002). An N-terminal Arginine-rich Cluster and a Proline-Alanine-Threonine Repeat Region Determine the Cellular Localization of the Herpes Simplex Virus Type 1 ICP34.5 Protein and Its Ligand, Protein Phosphatase 1. J. Biol. Chem. 277: 11423-11431 [Abstract] [Full Text]  
  • Cassady, K. A., Gross, M. (2002). The Herpes Simplex Virus Type 1 US11 Protein Interacts with Protein Kinase R in Infected Cells and Requires a 30-Amino-Acid Sequence Adjacent to a Kinase Substrate Domain. J. Virol. 76: 2029-2035 [Abstract] [Full Text]  
  • Cassady, K. A., Gross, M., Gillespie, G. Y., Roizman, B. (2002). Second-Site Mutation Outside of the US10-12 Domain of {Delta}{gamma}134.5 Herpes Simplex Virus 1 Recombinant Blocks the Shutoff of Protein Synthesis Induced by Activated Protein Kinase R and Partially Restores Neurovirulence. J. Virol. 76: 942-949 [Abstract] [Full Text]  
  • Taneja, S., MacGregor, J., Markus, S., Ha, S., Mohr, I. (2001). Enhanced antitumor efficacy of a herpes simplex virus mutant isolated by genetic selection in cancer cells. Proc. Natl. Acad. Sci. USA 10.1073/pnas.161011798v1 [Abstract] [Full Text]  
  • Taneja, S., MacGregor, J., Markus, S., Ha, S., Mohr, I. (2001). Enhanced antitumor efficacy of a herpes simplex virus mutant isolated by genetic selection in cancer cells. Proc. Natl. Acad. Sci. USA 98: 8804-8808 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»