CDK9 and SPT5 proteins are specifically required for expression of herpes simplex virus 1 replication-dependent late genes.
J Biol Chem
; 292(37): 15489-15500, 2017 09 15.
Article
em En
| MEDLINE
| ID: mdl-28743741
ABSTRACT
DNA replication greatly enhances expression of the herpes simplex virus 1 (HSV-1) γ2 late genes by still unknown mechanisms. Here, we demonstrate that 5,6-dichloro-1-ß-d-ribofuranosylbenzimidazole (DRB), an inhibitor of CDK9, suppresses expression of γ2 late genes with an IC50 of 5 µm, which is at least 10 times lower than the IC50 value required for inhibition of expression of early genes. The effect of DRB could not be explained by inhibition of DNA replication per se or loading of RNA polymerase II to late promoters and subsequent reduction of transcription. Instead, DRB reduces accumulation of γ2 late mRNA in the cytoplasm. In addition, we show that siRNA-mediated knockdown of the transcription factor SPT5, but not NELF-E, also gives rise to a specific inhibition of HSV-1 late gene expression. Finally, addition of DRB reduces co-immunoprecipitation of ICP27 using an anti-SPT5 antibody. Our results suggest that efficient expression of replication-dependent γ2 late genes is, at least in part, regulated by CDK9 dependent co- and/or post-transcriptional events involving SPT5 and ICP27.
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MEDLINE
Assunto principal:
Replicação Viral
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Proteínas Cromossômicas não Histona
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Regulação Viral da Expressão Gênica
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Proteínas Imediatamente Precoces
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Herpesvirus Humano 1
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Fatores de Elongação da Transcrição
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Quinase 9 Dependente de Ciclina
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Replicação do DNA
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article