Upregulation of Mouse Genes in HSV-1 Latent TG after Butyrate Treatment Implicates the Multiple Roles of the LAT-ICP0 Locus

Funding Source

National Institutes of Health, LSU Eye Center Core Grant for Vision Research,

Grant Number

EY006311, EY02377


Department of Biology

Document Type


Publication Date



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 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. RESULTS. Differential induction of gene expression between 17Syn+ and its mutant 17ΔPst(LAT-) was designated as NaBuinduced 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 stressinduction. 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.


DOI: 10.1167/iovs.09-5019

PubMed ID: 20881297