Upregulation of mouse genes in HSV-1 latent TG after butyrate treatment implicates the multiple roles of the LAT-ICP0 locus.
OBJECTIVE
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.
Clement
Christian
C
Department of Ophthalmology, LSU Eye Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA.
Bhattacharjee
Partha S
PS
Kumar
Manish
M
Foster
Timothy P
TP
Thompson
Hilary W
HW
Hill
James M
JM
D000818:Animals; D002087:Butyrates / Q000494:pharmacology*; D003315:Cornea / Q000294:innervation; D056915:DNA Copy Number Variations; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D015967:Gene Expression Regulation, Viral / Q000187:drug effects*; D018259:Herpesvirus 1, Human / Q000235:genetics* / Q000502:physiology; D006657:Histones / Q000378:metabolism; D017874:Immediate-Early Proteins / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000502:physiology*; D009707:Nucleosomes / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012668:Trigeminal Ganglion / Q000821:virology*; D044767:Ubiquitin-Protein Ligases / Q000502:physiology*; D015854:Up-Regulation; D014775:Virus Activation / Q000187:drug effects; D017735:Virus Latency / Q000502:physiology*
D002087:Butyrates; D004279:DNA, Viral; D006657:Histones; D017874:Immediate-Early Proteins; D035683:MicroRNAs; D009707:Nucleosomes; C477253:latency associated transcript, herpes simplex virus-1; D044767:Ubiquitin-Protein Ligases; C051804:Vmw110 protein, Human herpesvirus 1