DOI: 10.1128/jvi.75.11.5189-5196.2001. A Herpes Simplex Virus Type 1 γ34.5 Second-Site Suppressor Mutant That Exhibits Enhanced Growth in Cultured Glioblastoma Cells Is Severely Attenuated in Animals

A Herpes Simplex Virus Type 1 γ34.5 Second-Site Suppressor Mutant That Exhibits Enhanced Growth in Cultured Glioblastoma Cells Is Severely Attenuated in Animals

10.1128/jvi.75.11.5189-5196.2001

Crossref journal-article

American Society for Microbiology

Journal of Virology (235)

Abstract

ABSTRACT We describe here the neurovirulence properties of a herpes simplex virus type 1 γ34.5 second-site suppressor mutant. γ34.5 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 γ34.5 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 γ34.5 parent virus at the doses investigated. Repairing the γ34.5 mutation in the suppressor mutant restores neurovirulence to wild-type levels. These studies illustrate that (i) the protein synthesis and neurovirulence defects observed in γ34.5 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 γ34.5 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 γ34.5 second-site suppressor variant is attenuated and replicates vigorously in neoplastic cells, it may have potential as a replication-competent, viral antitumor agent.

Bibliography

Mohr, I., Sternberg, D., Ward, S., Leib, D., Mulvey, M., & Gluzman, Y. (2001). A Herpes Simplex Virus Type 1 Î³34.5 Second-Site Suppressor Mutant That Exhibits Enhanced Growth in Cultured Glioblastoma Cells Is Severely Attenuated in Animals. Journal of Virology, 75(11), 5189â5196.

Authors 6

Ian Mohr (first)
David Sternberg (additional)
Stephen Ward (additional)
David Leib (additional)
Matthew Mulvey (additional)
Yakov Gluzman (additional)

References 37 Referenced 78

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Andreansky S. Soroceanu L. Flotte E. R. Chou J. Markert J. M. Gillespie G. Y. Roizman B. Whitely R. J. Evaluation of genetically engineered herpes simplex viruses as oncolytic agents for human malignant brain tumors.Cancer Res. 57 1997 1502 1509 / Cancer Res. / Evaluation of genetically engineered herpes simplex viruses as oncolytic agents for human malignant brain tumors by Andreansky S. (1997)
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Dates

Type	When
Created	23 years, 1 month ago (July 27, 2002, 6:06 a.m.)
Deposited	3 years, 5 months ago (March 5, 2022, 12:58 a.m.)
Indexed	1 week, 5 days ago (Aug. 23, 2025, 12:59 a.m.)
Issued	24 years, 3 months ago (June 1, 2001)
Published	24 years, 3 months ago (June 1, 2001)
Published Print	24 years, 3 months ago (June 1, 2001)

Funders 0

None

BibTeX

@article{Mohr_2001, title={A Herpes Simplex Virus Type 1 γ34.5 Second-Site Suppressor Mutant That Exhibits Enhanced Growth in Cultured Glioblastoma Cells Is Severely Attenuated in Animals}, volume={75}, ISSN={1098-5514}, url={http://dx.doi.org/10.1128/jvi.75.11.5189-5196.2001}, DOI={10.1128/jvi.75.11.5189-5196.2001}, number={11}, journal={Journal of Virology}, publisher={American Society for Microbiology}, author={Mohr, Ian and Sternberg, David and Ward, Stephen and Leib, David and Mulvey, Matthew and Gluzman, Yakov}, year={2001}, month=jun, pages={5189–5196} }

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