Varicella induced transcriptional changes in the lung. Macaca mulatta

Host-pathogen interactions during acute varicella zoster virus (VZV) infection in the lungs remain poorly understood due to limited access to tissue biopsies from individuals during acute varicella infection. We leveraged a nonhuman primate model of VZV infection where rhesus macaques are intrabronchially challenged with the closely related simian varicella virus (SVV). Rhesus macaques were euthanized on days 3, 7, 10 and 14 post infection and lung and BAL tissue were used to conduct histological, flow cytometry and RNA-Seq analysis. Acute varicella infection resulted in immune infiltration of the lung airways, a significant up-regulation of genes involved in antiviral-immunity that correlated with viral loads, and a down-regulation of genes involved in lung development. Resolution of disease process was accompanied by a decrease in viral loads and increased expression of genes associated with tissue repair. Data presented in this manuscript provide the first characterization of the host innate and adaptive immune response required to control varicella virus replication in the lung. Our results show that acute varicella infection leads to lung injury even in an immune competent host, but once viral replication ceases, repair is initiated. These results provide novel insight into mechanisms by which VZV infection can cause lung injury and viral pneumonia and the host responses required to control viral replication in an immune competent host.