Characterization of the immune response in ganglia after primary simian varicella virus infection.

Werner J D Ouwendijk,Albert D M E Osterhaus,Sarah Getu,Don Gilden,Georges M G M Verjans,Ravi Mahalingam

doi:10.1007/s13365-015-0408-1

Abstract

Primary simian varicella virus (SVV) infection in non-human primates causes varicella, after which the virus becomes latent in ganglionic neurons and reactivates to cause zoster. The host response in ganglia during establishment of latency is ill-defined. Ganglia from five African green monkeys (AGMs) obtained at 9, 13, and 20 days post-intratracheal SVV inoculation (dpi) were analyzed by ex vivo flow cytometry, immunohistochemistry, and in situ hybridization. Ganglia at 13 and 20 dpi exhibited mild inflammation. Immune infiltrates consisted mostly of CD8dim and CD8bright memory T cells, some of which expressed granzyme B, and fewer CD11c+ and CD68+ cells. Chemoattractant CXCL10 transcripts were expressed in neurons and infiltrating inflammatory cells but did not co-localize with SVV open reading frame 63 (ORF63) RNA expression. Satellite glial cells expressed increased levels of activation markers CD68 and MHC class II at 13 and 20 dpi compared to those at 9 dpi. Overall, local immune responses emerged as viral DNA load in ganglia declined, suggesting that intra-ganglionic immunity contributes to restricting SVV replication.

Highlights

Varicella-zoster virus (VZV) is a neurotropic human alphaherpesvirus
In African green monkeys (AGMs) infected with simian varicella virus (SVV)-wt or SVV-EGFP, we demonstrated that SVV nucleocapsid antigen was more abundant in ganglia at 9 dpi compared to 13 and 20 dpi (Ouwendijk et al 2013b)
The significantly higher SVV DNA load and more abundant SVV nucleocapsid antigen expression in ganglia at 9 dpi compared to 13 and 20 dpi (Ouwendijk et al 2013b) suggest an initial phase of virus replication followed by establishment of latency

Summary

Introduction

Varicella-zoster virus (VZV) is a neurotropic human alphaherpesvirus. Primary infection causes varicella (chicken pox), after which VZV becomes latent in ganglionic neurons; reactivation leads to zoster (shingles) (Arvin and Gilden 2013). Virus-specific immunity is essential for uncomplicated recovery from varicella and zoster (Arvin and Gilden 2013). Zoster is associated with profound inflammation of ganglia, mainly involving infiltrating T cells that are likely to inhibit local VZV replication and spread (Gowrishankar et al 2010; Steain et al 2014). The immune response in human ganglia after primary VZV infection has not been studied in detail (Berg et al 1969; Cheatham et al 1956; Nagashima et al 1975)

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