Abstract
AimsTo understand the mechanisms of Early Growth Response Protein 1 (Egr-1) induction upon HSV-1 lytic infection and its roles in regulating viral gene expression and replication.Study DesignRabbit corneal cell line SIRC and other cell lines were infected by HSV-1 to investigate the Egr-1 induction and its occupancy on the viral genome in different conditions. UV-inactivated HSV-1 and a recombinant virus over-expressing Egr-1 were generated to evaluate the regulatory effects on viral gene expression and replication during the infection.MethodologyEgr-1 induction triggered by viral infection was determined by Western Blot analyses and immune-fluorescent microscopy. Real-time RT-PCR and a novel Cignal™ Reporter Assay were used for quantitative measurement of Egr-1 expression. Chromatin Immuno-precipitation (ChIP) was performed to address the Egr-1 occupancy to the viral regulatory sequences and the influence on viral replication was assessed by plaque assays.ResultsOur results indicated that Egr-1 expression requires viral gene expression since the UV-inactivated HSV-1 failed to produce Egr-1 protein. Blockade of viral replication did not block the Egr-1 protein synthesis, supporting the hypothesis that HSV-1 replication was not essential for Egr-1 production. Chromatin immune-precipitation (ChIP) and RT-PCR assays demonstrated that induced Egr-1 was able to interact with key regulatory elements near HSV-1 immediate-early (IE) genes and promote viral gene expression. Recombinant virus overexpressing Egr-1 revealed that Egr-1 enhanced the viral replication and the release of infectious virus.ConclusionTogether these results concluded that HSV-1 triggers the expression of an important host transcription factor Egr-1 via a unique mechanism and benefit the viral gene expression and replication.
Highlights
HSV-1 developed many strategies to infect a broad range of human cell types
Our results indicated that Early Growth Response type-1 (Egr-1) expression requires viral gene expression since the UV-inactivated HSV-1 failed to produce Egr-1 protein
Together these results concluded that HSV-1 triggers the expression of an important host transcription factor Egr-1 via a unique mechanism and benefit the viral gene expression and replication
Summary
HSV-1 developed many strategies to infect a broad range of human cell types. During infections the virus decomposed host RNA and turned off protein synthesis efficiently[1]. Certain host proteins were not present but rapidly produced after the entry of virus into the cells. Growth Response type-1 (Egr-1) is one of the proteins that belong to this group]2]. Egr-1 is a Zinc finger binding protein that has many different names such as Nerve Growth Factor-Induced gene A (NGFI-A), Zinc finger binding protein clone 286 (zif268), etc. Egr-1 is a member of the immediate early gene superfamily, whose presence is robust and transient in the cell shortly after the stimulation without de novo protein synthesis[3]. The gene product codes for a transcription factor, preferentially binds to the GC-rich sequence 5′-GCGGGGGCG-3′ [4]
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