Negative regulation of herpes simplex virus type 1 ICP4 promoter by IE180 protein of pseudorabies virus.
Recombinant pseudorabies viruses (PRVs) gIS8 and N1aHTK were constructed by the insertion of a chimeric gene (alpha4-TK) from herpes simplex virus type 1 (HSV-1) into wild-type PRV. HSV-1 TK expression by these recombinant viruses resulted in enhanced sensitivity to ganciclovir, compared to that of the wild-type PRV, and was similar to the sensitivity shown by HSV-1. Infection with gIS8 or N1aHTK recombinant viruses led to expression of HSV-1 TK mRNA as an immediate-early (IE) gene, observed by downregulation of the HSV-1 alpha4 promoter. This negative regulation was due to a PRV IE protein, IE180. IE180, however, does not have all the regulatory functions of the infected-cell protein ICP4, as it does not restore the growth of ICP4-deficient HSV-1 mutants.
Gómez-Sebastián
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Departamento de Medicina Preventiva, Salud Pública y Microbiología, Facultad de Medicina, Universidad Autónoma de Madrid, Arzobispo Morcillo 4, E-28029 Madrid, Spain.
Tabarés
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Departamento de Medicina Preventiva, Salud Pública y Microbiología, Facultad de Medicina, Universidad Autónoma de Madrid, Arzobispo Morcillo 4, E-28029 Madrid, Spain.
D015774:Ganciclovir / Q000494:pharmacology; D015967:Gene Expression Regulation, Viral; D017874:Immediate-Early Proteins / Q000235:genetics* / Q000502:physiology*; D011401:Promoter Regions, Genetic
D017874:Immediate-Early Proteins; C048925:herpes simplex virus, type 1 protein ICP4; C047583:pseudorabies virus immediate early proteins; D015774:Ganciclovir