Heat-induced reactivation of HSV-1 in latent mice: upregulation in the TG of CD83 and other immune response genes and their LAT-ICP0 locus.
OBJECTIVE
To determine changes in host gene expression in HSV-1 latent trigeminal ganglia (TG) after hyperthermic stress.


METHODS
Scarified corneas of 6-week-old female BALB/c mice were inoculated with either HSV-1 17Syn(+) (high phenotypic reactivator) or 17DeltaPst(LAT(-)) (low phenotypic reactivator) at 10(4) plaque-forming units/eye. At 28 days after infection, viral reactivation was induced in some of the infected mice with hyperthermic stress, and the mice were killed after 1 hour. Heat-treated uninfected mice served as the control. Labeled cRNA derived from TG-isolated total RNA was hybridized to 430 2.0 chips containing 14,000 mouse genes. Gene expression was confirmed by quantitative real-time PCR.


RESULTS
There was no difference in gene expression in the non-heat-treated mice. Gene expression in the TG of each of the heat-treated mouse groups (17Syn(+), 17DeltaPst(LAT(-)) and uninfected) yielded upregulation of more than twofold of a group of the same genes, designated as heat stress-induced gene expression. Twenty-nine genes (0.2%) were significantly upregulated (2- to 17-fold) when the heat stress-induced gene expression was subtracted from the gene expression of 17Syn(+) latent TG relative to 17DeltaPst(LAT(-)) latent TG 1 hour after mouse hyperthermic stress. Nine host adaptive immunity genes comprising Ig molecules, CD83, CD8A, ADA, and CCL8 were the largest subset upregulated, and all were confirmed by real-time PCR. Others identified included genes involved in hypothalamic-pituitary gland functions.


CONCLUSIONS
Hyperthermic stress-induced reactivation of the HSV-1 high phenotypic reactivator can upregulate gene expression involved in B-cell function and in T-cell function. CD83 is implicated in HSV-1 latency, suggesting it could also be involved in immune-mediated mechanisms of viral reactivation.
Clement
Christian
C
Department of Ophthalmology, LSU Eye Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, USA.
Bhattacharjee
Partha S
PS
Kaufman
Herbert E
HE
Hill
James M
JM
D051997:ADP-ribosyl Cyclase 1 / Q000235:genetics*; D000818:Animals; D016827:CD8 Antigens / Q000235:genetics; D054412:Chemokine CCL8 / Q000235:genetics; D003315:Cornea / Q000294:innervation* / Q000821:virology; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D005802:Genes, MHC Class II / Q000235:genetics*; D018259:Herpesvirus 1, Human / Q000502:physiology*; D006358:Hot Temperature; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013312:Stress, Physiological; D012668:Trigeminal Ganglion / Q000821:virology*; D014775:Virus Activation
D016827:CD8 Antigens; C409469:CD8 antigen, alpha chain; C515454:Ccl8 protein, mouse; D054412:Chemokine CCL8; D008562:Membrane Glycoproteins; D035683:MicroRNAs; C477253:latency associated transcript, herpes simplex virus-1; C498155:Cd38 protein, mouse; D051997:ADP-ribosyl Cyclase 1