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Christian Clement, Partha S. Bhattacharjee, Manish Kumar, Timothy P. Foster, Hilary W. Thompson, James M. Hill; Upregulation of Mouse Genes in HSV-1 Latent TG after Butyrate Treatment Implicates the Multiple Roles of the LAT-ICP0 Locus. Invest. Ophthalmol. Vis. Sci. 2011;52(3):1770-1779. doi: 10.1167/iovs.09-5019.
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© ARVO (1962-2015); The Authors (2016-present)
To determine host response by gene expression in HSV-1 latent trigeminal ganglia (TG) after sodium butyrate (NaBu) treatment.
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 104 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.
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).
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.
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