Varicella-Zoster virus gene expression in latently infected rat dorsal root ganglia

Latent infection of human ganglia with Varicella-Zoster virus (VZV) is char acterized by a highly restricted pattern of viral gene expression. To enhan ce understanding of this process we used in situ hybridization (ISH) In a r at model of VZV latency to examine expression of RNA corresponding to eight different VZV genes in rat dorsal root ganglia (DRG) at various times afte r footpad inoculation with wild-type VZV. PCR in situ amplification was als o used to determine the cell specificity of latent VZV DNA. It was found th at the pattern of viral gene expression at 1 week after infection was diffe rent from that observed at the later times of 1 and 18 months after infecti on. Whereas multiple genes were expressed at 1 week after infection, gene e xpression was restricted at the later time points when latency had been est ablished. At the later time points after infection the RNA transcripts expr essed most frequently were those for VZV genes 21, 62, and 63, Gene 63 was expressed more than any other gene studied. While VZV DNA was detected almo st exclusively in 5-10% of neurons, VZV RNA was detected in both neurons an d nonneuronal cells at an approximate ratio of 3:1. A newly described monoc lonal antibody to VZV gene 63-encoded protein was used to detect this prote in in neuronal nuclei and cytoplasm in almost half of the DRG studied. Thes e results demonstrate that (1) this rat model of latency has close similari ties in terms of viral gene expression to human VZV latency which makes it a useful tool for studying this process and its experimental modulation and (2) expression of Vzv gene 63 appears to be the single most consistent fea ture of VZV latency. (C) 2001 Academic Press.