Transcriptional and functional remodeling of lung-resident T cells and macrophages by Simian Varicella Virus infection

Human varicella zoster virus (VZV) is the causative agent of varicella (acute infection) and herpes zoster (reactivation). VZV is transmitted via the respiratory route yet establishes latency in sensory ganglia by mechanisms poorly understood but believed to use T cells and macrophages for dissemination. We leveraged a rhesus macaque model where animals are intrabronchially inoculated with Simian varicella virus (SVV), a VZV homologue, to compare the transcriptome of infected and bystander cells at the single cell resolution. Single cell RNA-seq analysis showed an a decrease in alveolar macrophages concomitant with an increase in infiltrating macrophages harboring an antiviral signature, proliferating T cells, effector CD8+ T cells, and GRZMA+ T cells. Comparative analysis of infected and bystander cells revealed higher expression of viral genes in infected T cells compared to macrophages. Additionally, genes important for cellular metabolism (glycolysis and oxidative phosphorylation) were differentially expressed suggesting adaptations to viral replication. These distinct molecular changes occurring within infected cells may facilitate viral dissemination from the respiratory tract to sensory ganglia.