Acute simian varicella infection causes robust and sustained changes in gene expression in the sensory ganglia. Macaca mulatta

Varicella zoster virus (VZV) is a neurotropic alpha herpesvirus that causes varicella (chickenpox) during primary infection. VZV establishes latency in the sensory ganglia and can reactivate later in life to cause herpes zoster (shingles). The relationship between the virus and host during acute infection in the sensory ganglia is not well understood due to limited access to clinical specimens. However, intrabronchial inoculation of rhesus macaques with simian varicella virus (SVV), a homolog of VZV, recapitulates the hallmarks of VZV infection in humans. In this study, we used to this animal model to characterize the host-pathogen interactions in the ganglia during both acute and latent infection by measuring both viral and host transcriptomes at days 3, 7, 10, 14 and 100-post infection. Here, we show both SVV viral DNA and transcripts are detected in the sensory ganglia as early as day 3-post infection, before the establishment of latency at day 7-post infection. We further show that SVV DNA is primarily carried in the CD4 and CD8 T cells in the BAL and supports replication. Illumina RNA-Seq analysis shows that cessation of viral replication coincides with the development of a robust antiviral innate immune response in the ganglia. Finally, a significant number of genes that play a critical role in nervous system development and function remained down regulated into latency. These data demonstrate that SVV infection of the sensory ganglia results in profound and sustained changes in neuronal gene expression. These studies provide the first insights into the viral replication kinetics and host response in the sensory ganglia during acute varicella and enhance our understanding of the neurological complications caused by VZV.