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Volume 73, Issue 11

Antiviral properties of a dominant negative mutant of the herpes simplex virus type 1 regulatory protein ICP0 Free

Abstract

Dominant negative or trans-dominant mutants of viral proteins represent a new and exciting potential approach to antiviral therapy. Unfortunately, the extreme specificity of a given dominant negative mutant limits its general utility in treating a broad spectrum of viral diseases, since it can typically interfere with the activity of only a single viral polypeptide encoded by a single virus. However, it seems likely that dominant negative mutants of promiscuous viral trans-activator proteins, which by definition would repress rather than activate gene expression, should be able to inhibit infectious virus production for a number of different viruses. One such dominant negative mutant, derived from the herpes simplex virus type 1 (HSV-1) regulatory protein ICP0, was found previously to behave as a powerful repressor of gene expression from an assortment of HSV-1 and non-HSV-1 promoters in transient expression assays. In the present study, this ICP0 mutant was found to be capable of inhibiting the replication of both HSV-1 and a completely unrelated virus, human immunodeficiency virus, in cell culture. The properties of this dominant negative mutant indicate that it may have potential as a means of treating diseases caused by a number of DNA and RNA viruses. Moreover, a truncated form of ICP0 which can hypothetically be created by alternative splicing was found to possess similar inhibitory capabilities, suggesting that a virus-encoded version of this dominant negative mutant may play a role in down-regulating HSV-1 gene expression during infection .

  • Received:
  • Accepted:
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© Journal of General Virology 1992
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1992-11-01
2024-04-19
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Antiviral properties of a dominant negative mutant of the herpes simplex virus type 1 regulatory protein ICP0
J. Gen. Virol. 73, 2955 (1992); https://doi.org/10.1099/0022-1317-73-11-2955
/content/journal/jgv/10.1099/0022-1317-73-11-2955
/content/journal/jgv/10.1099/0022-1317-73-11-2955
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