Upregulation of mouse genes in HSV-1 latent TG after butyrate treatment implicates the multiple roles of the LAT-ICP0 locus.
| Autor: | Clement C; Department of Ophthalmology, LSU Eye Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA., Bhattacharjee PS, Kumar M, Foster TP, Thompson HW, Hill JM |
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| Jazyk: | angličtina |
| Zdroj: | Investigative ophthalmology & visual science [Invest Ophthalmol Vis Sci] 2011 Mar 28; Vol. 52 (3), pp. 1770-9. Date of Electronic Publication: 2011 Mar 28 (Print Publication: 2011). |
| DOI: | 10.1167/iovs.09-5019 |
| Abstrakt: | 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 17ΔPst(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 17ΔPst(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. |
| Databáze: | MEDLINE |
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