Abstract
Purpose: :
Herpes simplex virus type-1 (HSV-1) lytic infection causes diseases ranging from simple cold sores to dangerous keratitis and lethal encephalitis. The interaction between virus and host cells is being investigated extensively by many laboratories. In this study, we demonstrated that HSV-1 can rapidly induce the expression of multi functional transcriptional factor early growth response-1 (Egr-1) during lytic infection.
Methods: :
This study utilized various cell/molecular biology techniques such as Western blot, RTPCR, immunofluorescent microscopy, chromatin immunoprecipitation (ChIP), etc to address the specific questions.
Results: :
Western blot analyses showed that Egr-1 was absent in a rabbit corneal cell line SIRC but the protein was detected starting from 24 hours post infection (hpi) and was directly proportional to the amount of virus used for infection. Infection of cells with recombinant virus expressing EGFP followed by immunofluorescent studies revealed that Egr1 was expressed only within the infected cells. ChIP assays demonstrated that NFkB and cAMP response element binding protein (CREB) were recruited to the Egr-1 promoter upon infection. Additional studies showed that NFkB inhibitor and dominant-negative CREB repressed the Egr1 induction by HSV-1 infection, suggesting that these two factors participated in the induction.
Conclusions: :
Collectively, these results showed that Egr-1 is efficiently induced upon HSV-1 infection and may be due to the NFkB/CREB- mediated transactivation. Egr-1 induction may play a key role in the viral gene expression, replication, inflammation, and the disease progression.
Keywords: herpes simplex virus • cornea: basic science • gene/expression