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Science 30 November 1990:
Vol. 250. no. 4985, pp. 1262 - 1266
DOI: 10.1126/science.2173860

Articles

Science, Vol 250, Issue 4985, 1262-1266
Copyright © 1990 by American Association for the Advancement of Science


articles

Mapping of herpes simplex virus-1 neurovirulence to gamma 134.5, a gene nonessential for growth in culture

J Chou, ER Kern, RJ Whitley, and B Roizman

Marjorie B. Kovler Viral Oncology Laboratories, University of Chicago, IL 60637.

The gene designated gamma 134.5 maps in the inverted repeats flanking the long unique sequence of herpes simplex virus-1 (HSV-1) DNA, and therefore it is present in two copies per genome. This gene is not essential for viral growth in cell culture. Four recombinant viruses were genetically engineered to test the function of this gene. These were (i) a virus from which both copies of the gene were deleted, (ii) a virus containing a stop codon in both copies of the gene, (iii) a virus containing after the first codon an insert encoding a 16-amino acid epitope known to react with a specific monoclonal antibody, and (iv) a virus in which the deleted sequences were restored. The viruses from which the gene was deleted or which carried stop codons were avirulent on intracerebral inoculation of mice. The virus with the gene tagged by the sequence encoding the epitope was moderately virulent, whereas the restored virus reacquired the phenotype of the parent virus. Significant amounts of virus were recovered only from brains of animals inoculated with virulent viruses. Inasmuch as the product of the gamma 134.5 gene extended the host range of the virus by enabling it to replicate and destroy brain cells, it is a viral neurovirulence factor.


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N. N. Khodarev, S. J. Advani, N. Gupta, B. Roizman, and R. R. Weichselbaum (1999)
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Ionizing Radiation Improves Survival in Mice Bearing Intracranial High-Grade Gliomas Injected with Genetically Modified Herpes Simplex Virus.
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Replication-competent, Nonneuroinvasive Genetically Engineered Herpes Virus Is Highly Effective in the Treatment of Therapy-resistant Experimental Human Tumors.
S. J. Advani, S.-M. Chung, S. Y. Yan, G. Y. Gillespie, J. M. Markert, R. J. Whitley, B. Roizman, and R. R. Weichselbaum (1999)
Cancer Res. 59, 2055-2058
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Interferons Regulate the Phenotype of  Wild-type and Mutant Herpes Simplex Viruses In Vivo.
D. A. Leib, T. E. Harrison, K. M. Laslo, M. A. Machalek, N. J. Moorman, and H. W. Virgin (1999)
J. Exp. Med. 189, 663-672
   Abstract »    Full Text »    PDF »
The Herpes Simplex Virus US11 Protein Effectively Compensates for the gamma 134.5 Gene if Present before Activation of Protein Kinase R by Precluding Its Phosphorylation and That of the alpha  Subunit of Eukaryotic Translation Initiation Factor 2.
K. A. Cassady, M. Gross, and B. Roizman (1998)
J. Virol. 72, 8620-8626
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The Second-Site Mutation in the Herpes Simplex Virus Recombinants Lacking the gamma 134.5 Genes Precludes Shutoff of Protein Synthesis by Blocking the Phosphorylation of eIF-2alpha.
K. A. Cassady, M. Gross, and B. Roizman (1998)
J. Virol. 72, 7005-7011
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The Polyserine Tract of Herpes Simplex Virus ICP4 Is Required for Normal Viral Gene Expression and Growth in Murine Trigeminal Ganglia.
P. A. Bates and N. A. DeLuca (1998)
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The gamma 134.5 Protein of Herpes Simplex Virus 1 Has the Structural and Functional Attributes of a Protein Phosphatase 1 Regulatory Subunit and Is Present in a High Molecular Weight Complex with the Enzyme in Infected Cells.
B. He, M. Gross, and B. Roizman (1998)
J. Biol. Chem. 273, 20737-20743
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A Virus with a Mutation in the ICP4-Binding Site in the L/ST Promoter of Herpes Simplex Virus Type 1, but Not a Virus with a Mutation in Open Reading Frame P, Exhibits Cell-Type-Specific Expression of gamma 134.5 Transcripts and Latency-Associated Transcripts.
L. Y. Lee and P. A. Schaffer (1998)
J. Virol. 72, 4250-4264
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Virus Attenuation after Deletion of the Cytomegalovirus Fc Receptor Gene Is Not due to Antibody Control.
I. Crnkovic-Mertens, M. Messerle, U. Szepan, and U. H. Koszinowski (1998)
J. Virol. 72, 1377-1382
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The gamma 134.5 protein of herpes simplex virus 1 complexes with protein phosphatase 1alpha to dephosphorylate the alpha  subunit of the eukaryotic translation initiation factor 2 and preclude the shutoff of protein synthesis by double-stranded RNA-activated protein kinase.
B. He, M. Gross, and B. Roizman (1997)
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S. Kesari, V. M.-Y. Lee, S. M. Brown, J. Q. Trojanowski, and N. W. Fraser (1996)
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From the Cover: Specific phenotypic restoration of an attenuated virus by knockout of a host resistance gene.
D. A. Leib, M. A. Machalek, B. R. G. Williams, R. H. Silverman, and H. W. Virgin (2000)
PNAS 97, 6097-6101
   Abstract »    Full Text »    PDF »
Oncolytic herpes simplex virus vector with enhanced MHC class I presentation and tumor cell killing.
T. Todo, R. L. Martuza, S. D. Rabkin, and P. A. Johnson (2001)
PNAS 98, 6396-6401
   Abstract »    Full Text »    PDF »
Enhanced antitumor efficacy of a herpes simplex virus mutant isolated by genetic selection in cancer cells.
S. Taneja, J. MacGregor, S. Markus, S. Ha, and I. Mohr (2001)
PNAS 98, 8804-8808
   Abstract »    Full Text »    PDF »
The Ebola virus VP35 protein functions as a type I IFN antagonist.
C. F. Basler, X. Wang, E. Muhlberger, V. Volchkov, J. Paragas, H.-D. Klenk, A. Garcia-Sastre, and P. Palese (2000)
PNAS 97, 12289-12294
   Abstract »    Full Text »    PDF »



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Science. ISSN 0036-8075 (print), 1095-9203 (online)