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


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PURPOSE. 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 17δPst(LAT-) (low phenotypic reactivator) at 104 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+, 17δPst(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 17δPst(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.


DOI: 10.1167/iovs.08-2430

PubMed ID: 19151393