Gene expression analyzed by microarrays in HSV-1 latent mouse trigeminal ganglion following heat stress

An understanding of the cellular genes whose expression is altered during H SV reactivation will enable us to better understand host responses and bioc hemical pathways involved in the process. Furthermore, this knowledge could allow us to develop gene-targeted inhibitors to prevent viral reactivation . Mice latent with HSV-1 strain McKrae and uninfected control mice were sub jected to hyperthermic stress (43 degreesC for 10 min) and their trigeminal ganglia (TG) collected 1 h later. Two additional groups included HSV-1 lat ently infected and uninfected mice not subjected to hyperthermic stress. Po ly A+ mRNA was enriched from total mouse TG RNA and reverse transcribed usi ng MMLV RT. Radioactively labeled cDNAs were analyzed by microarray analysi s. A stress/toxicology array of 149 mouse genes on a nylon membrane was use d. The labeled cDNAs prepared from latently infected, stressed mice demonst rated 3-fold or greater increases in certain mRNA-early response genes (ERG s) compared to cDNAs from uninfected, stressed control mice. The ERG mRNAs that showed increases included two heat shock proteins (HSP60 and HSP40), a basic transcription factor (BTF T62), a DNA repair enzyme, two kinases [MA P kinase and a stress-induced protein kinase (SADK)], an oxidative stress-i nduced protein, a manganese superoxide dismutase precursor-2 (SOD-2), and c yclooxygenase 2 (COX-2). The gene expression in unstressed, infected TGs wa s similar to the gene expression in unstressed, uninfected controls. These results suggest that there is a significant difference in the ERG expressio n profile in latently infected TGs undergoing stress-induced reactivation c ompared to uninfected TGs.