The DNA sequences required for the regulated expression of the HSV-1 glycoprotein D gene are located within 83 base pairs upstream of the RNA cap-sites.
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May refine HSV-1 vector design; leaves open clinical translation from animal models.
The genes of Herpes simplex virus type 1 (HSV-1) are classified into three temporally regulated groups. The Immediate-Early (IE) genes are transcribed first by the pre-existing transcription apparatus of the cell. The Early genes are transcribed only after IE-gene expression, and finally the Late genes are activated. The control of transcription of the HSV-1 glycoprotein D (gD) gene (an Early function) was studied by quantitative S1 mapping of RNA produced in HSV-1 infected HeLa cells after short-term transfection experiments using plasmids containing the gD promoter linked to the rabbit beta-globin gene. The viral promoter in the plasmid was activated in the same way as that in the virus itself; the RNA showed a similar time-course of appearance, dependence on prior IE-gene expression and pattern of RNA cap-sites. Deletion analysis showed that the DNA sequences necessary for Early promoter activation lie within 83 bp of the RNA cap-sites in this instance. Surprisingly, a plasmid-borne beta-globin promoter was also activated by HSV-1 infection. The mechanism of this activation, and DNA sequence similarities between the promoters of HSV-1 Early and rabbit beta-globin genes are discussed.
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Roger D. Everett (1983) studied this question.
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