Abstract

Simian varicella virus (SVV) infection of non-human primates is the counterpart of varicella zoster virus (VZV) infection in humans. To develop non-invasive methods of assessing SVV infection, we tested for the presence of SVV DNA in saliva, as has been documented in human VZV infection, and in buccal cells to determine whether epithelial cells might provide a more reliable source of material for analysis. Five rhesus macaques intratracheally inoculated with SVV all developed varicella with viremia and macular-papular skin rash in 1–2 weeks, which resolved followed by establishment of latency. DNA extracted from longitudinal blood peripheral blood mononuclear cells (PBMCs), saliva and buccal samples collected during acute infection and establishment of latency were analyzed by real-time qPCR. After intratracheal inoculation, viremia was observed, with peak levels of 101–102 copies of SVV DNA in 100 ng of PBMC DNA at 4 and 7 days post inoculation (dpi), which then decreased at 9–56 dpi. In saliva and buccal cells at 7 dpi, 101–104 copies and 101–105 copies of SVV DNA in 100 ng of cellular DNA, respectively, were detected in all the five monkeys. At 9 dpi, saliva samples from only two of the five monkeys contained SVV DNA at 102–103 copies/100 ng of saliva DNA, while buccal cells from all five monkeys showed 100–103 copies of SVV DNA/100 ng of buccal cell DNA. Similar to viremia, SVV DNA in saliva and buccal cells at 11–56 dpi was lower, suggesting clearance of viral shedding. SVV DNA levels were generally higher in buccal cells than in saliva. Our findings indicate that SVV shedding into the oral cavity parallels acute SVV infection and underscore the relevance of both saliva and buccal cell samples to monitor acute varicella virus infection.

Highlights

  • Simian varicella virus (SVV) infection of non-human primates (NHP) is the simian counterpart of varicella zoster virus (VZV) infection in humans

  • The SVV infection in NHP has been an extremely valuable animal model to further study the pathobiology and neurotropism of VZV showing virus entering ganglia before the appearance of primary rash; viral transport is via both hematogenous and non-hematogenous routes, critical gene expression, and cell signaling changes associated with disease; tropism of ganglionic, epithelial, and T lymphocytes (Mahalingam et al, 2001; Ouwendijk et al, 2013; Traina-Dorge et al, 2015, 2019; Arnold et al, 2016)

  • Our goal here was the development of a non-invasive method to analyze SVV infection and viremia after acute infection in non-human primates

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Summary

Introduction

Simian varicella virus (SVV) infection of non-human primates (NHP) is the simian counterpart of varicella zoster virus (VZV) infection in humans. Similar to primary VZV infection in humans, NHPs experimentally infected with SVV, develop acute varicella with malaise, fever, viremia, and generalized vesicular rash (Messaoudi et al, 2009; Ouwendijk et al, 2013). The SVV infection in NHP has been an extremely valuable animal model to further study the pathobiology and neurotropism of VZV showing virus entering ganglia before the appearance of primary rash; viral transport is via both hematogenous and non-hematogenous routes, critical gene expression, and cell signaling changes associated with disease; tropism of ganglionic, epithelial, and T lymphocytes (Mahalingam et al, 2001; Ouwendijk et al, 2013; Traina-Dorge et al, 2015, 2019; Arnold et al, 2016). We analyzed buccal cells for SVV DNA to determine whether buccal epithelial cells from anesthetized animals could provide a more reliable source of material

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