changes to euchromatin on lat and icp4 following reactivation are more prevalent in an efficiently reactivating strain of hsv-1改变常染色质lat和icp4复活后在1型单纯疱疹病毒的有效地重新激活应变.pdfVIP

Changes to Euchromatin on LAT and ICP4 Following Reactivation Are More Prevalent in an Efficiently Reactivating Strain of HSV-1 1 1,2 Clinton C. Creech , Donna M. Neumann * 1 Department of Ophthalmology (LSU Eye Center of Excellence), Louisiana State University Health Sciences Center, New Orleans, Louisiana, United States of America, 2 Department of Genetics, Louisiana State University Health Sciences Center, New Orleans, Louisiana, United States of America Abstract Background: Epigenetic mechanisms, via post-translational histone modifications, have roles in the establishment and maintenance of latency of the HSV-1 genome in the sensory neurons. Considering that many post-translational histone marks are reversible in nature, epigenetic mechanisms may also play a critical role in the process of induced HSV-1 reactivation. Methodology/Principal Findings: This study utilized the rabbit ocular model of HSV-1 infection and reactivation, induced by the transcorneal iontophoresis of epinephrine (TCIE), to characterize changes to chromatin that occur between 0.5 and 4 h following the application of the reactivation stimulus. Our goal was to explore the hypothesis that chromatin remodeling is an early and essential step in the process of HSV-1 reactivation. Analysis of the HSV-1 latently infected rabbit trigeminal ganglia (TG) showed that enrichment of the euchromatic marker H3K4me2 significantly decreased in the LAT 59exon region (,2.5-fold) and significantly increased in the lytic ICP4 promoter region (,3-fold) by 1 h post-TCIE in the highly efficient reactivating McKrae strain of HSV-1. In contrast, we observed no significant change in the euchromatic marks of H3K4me2 associated with LAT 59exon or ICP4 promoter regi