Varicella–Zoster virus proteins encoded by open reading frames 14 and 67 are both dispensable for the establishment of latency in a rat model

A rat model of Varicella–Zoster virus (VZV) provides a system in which to investigate the molecular determinants of viral latency in dorsal root ganglia (DRG). In this study, we determined whether the VZV glycoproteins gC and gI, corresponding to VZV open reading frames (ORFs) 14 and 67, respectively, were required for the establishment of latency in this model. A VZV gI deletion mutant (ΔgI) derived from a recombinant Oka (rOka) cosmid and a gC null mutant obtained from a clinical isolate were inoculated into the footpads of 6-week-old rats, and the presence of viral DNA and eight different VZV RNA transcripts corresponding to the three classes of genes was investigated by in situ RT-PCR amplification and in situ hybridization (ISH) in the DRG at 1 week, 1 month, and 18–24 months after infection. VZV DNA and restricted RNA expression was established with both deletion mutants as well as the parental rOka virus. Both VZV DNA and RNA were detected in neurons and non-neuronal cells. The pattern of viral RNA expression detected with both gC and gI mutants was restricted with transcripts for VZV genes 62 and 63 most frequently expressed 18–24 months after infection. Transcripts for VZV genes 18, 28, and 29 were also detected at these time points but at a slightly lower frequency. Transcripts for the late gene 40 were never detected. We conclude that VZV ORFs 14 and 67 are dispensable for the establishment of a latent infection in this model.