PMID- 20881297 OWN - NLM STAT- MEDLINE DCOM- 20110524 LR - 20211020 IS - 1552-5783 (Electronic) IS - 0146-0404 (Print) IS - 0146-0404 (Linking) VI - 52 IP - 3 DP - 2011 Mar TI - Upregulation of mouse genes in HSV-1 latent TG after butyrate treatment implicates the multiple roles of the LAT-ICP0 locus. PG - 1770-9 LID - 10.1167/iovs.09-5019 [doi] AB - PURPOSE: To determine host response by gene expression in HSV-1 latent trigeminal ganglia (TG) after sodium butyrate (NaBu) treatment. METHODS: Corneas of 6-week-old female BALB/c mice were scarified and inoculated with HSV-1 17Syn(+) (high phenotypic reactivator) or its mutant 17DeltaPst(LAT(-)) (low phenotypic reactivator) at 10(4) plaque-forming units/eye. NaBu-induced viral reactivation was by intraperitoneal (IP) administration at postinfection (PI) day 28, followed by euthanasia after 1 hour. NaBu-treated, uninfected mice served as the control. The resultant labeled cRNA from TG isolated total RNA was hybridized to gene microarray chips containing 14,000 mouse genes. Quantitative real-time PCR was performed to confirm gene expression. RESULTS: Differential induction of gene expression between 17Syn(+) and its mutant 17DeltaPst(LAT(-)) was designated as NaBu-induced gene expression and yielded significant upregulation of 2- to 16-fold of 0.4% (56/14,000) host genes probed, comprising mainly nucleosome assembly and binding, central nervous system structural activity, hormonal activity, and signaling activity. Approximately 0.2% (24/14,000) of the host genes, mainly of the same functional categories were downregulated 3- to 11-fold. Immune activity was minor in comparison to our reports on gene expression during latency and heat stress induction. Euchromatin analysis revealed that the LAT-ICP0 locus is amenable to the effects of NaBu. Histone activity was detected by early transcription of histone cluster 2 H2be (Hist2h2be). CONCLUSIONS NaBu-induced reactivation of HSV-1 is twofold: drug action involving significant moderation of specific host epigenetic changes and failure to elicit or suppress immune activity at the early time point of 1 hour. FAU - Clement, Christian AU - Clement C AD - Department of Ophthalmology, LSU Eye Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA. FAU - Bhattacharjee, Partha S AU - Bhattacharjee PS FAU - Kumar, Manish AU - Kumar M FAU - Foster, Timothy P AU - Foster TP FAU - Thompson, Hilary W AU - Thompson HW FAU - Hill, James M AU - Hill JM LA - eng GR - P30 EY002377/EY/NEI NIH HHS/United States GR - R01 EY006311/EY/NEI NIH HHS/United States GR - EY02377/EY/NEI NIH HHS/United States GR - EY006311/EY/NEI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20110328 PL - United States TA - Invest Ophthalmol Vis Sci JT - Investigative ophthalmology & visual science JID - 7703701 RN - 0 (Butyrates) RN - 0 (DNA, Viral) RN - 0 (Histones) RN - 0 (Immediate-Early Proteins) RN - 0 (MicroRNAs) RN - 0 (Nucleosomes) RN - 0 (latency associated transcript, herpes simplex virus-1) RN - EC 2.3.2.27 (Ubiquitin-Protein Ligases) RN - EC 2.3.2.27 (Vmw110 protein, Human herpesvirus 1) SB - IM MH - Animals MH - Butyrates/*pharmacology MH - Cornea/innervation MH - DNA Copy Number Variations MH - DNA, Viral/genetics MH - Female MH - Gene Expression Regulation, Viral/*drug effects MH - Herpesvirus 1, Human/*genetics/physiology MH - Histones/metabolism MH - Immediate-Early Proteins/*physiology MH - Mice MH - Mice, Inbred BALB C MH - MicroRNAs/*physiology MH - Nucleosomes/metabolism MH - Oligonucleotide Array Sequence Analysis MH - Reverse Transcriptase Polymerase Chain Reaction MH - Trigeminal Ganglion/*virology MH - Ubiquitin-Protein Ligases/*physiology MH - Up-Regulation MH - Virus Activation/drug effects MH - Virus Latency/*physiology PMC - PMC3101669 EDAT- 2010/10/01 06:00 MHDA- 2011/05/25 06:00 PMCR- 2012/03/01 CRDT- 2010/10/01 06:00 PHST- 2010/10/01 06:00 [entrez] PHST- 2010/10/01 06:00 [pubmed] PHST- 2011/05/25 06:00 [medline] PHST- 2012/03/01 00:00 [pmc-release] AID - iovs.09-5019 [pii] AID - 09-5019 [pii] AID - 10.1167/iovs.09-5019 [doi] PST - epublish SO - Invest Ophthalmol Vis Sci. 2011 Mar 28;52(3):1770-9. doi: 10.1167/iovs.09-5019. Print 2011 Mar.