Varicella-zoster virus proteome-wide T-cell screening demonstrates low prevalence of virus-specific CD8 T-cells in latently infected human trigeminal ganglia

• Published in: Journal of neuroinflammation Vol. 20; no. 1; pp. 141 - 12
• Main Authors: van Gent, Michiel, Ouwendijk, Werner J. D., Campbell, Victoria L., Laing, Kerry J., Verjans, Georges M. G. M., Koelle, David M.
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 12.06.2023; BioMed Central; BMC
• Subjects: Adult; Antibodies; Antigens; CD8 antigen; CD8-Positive T-Lymphocytes; Cell lines; Cells; Chicken pox; Cloning; Complications and side effects; Diagnosis; Epitopes; Flow cytometry; Ganglia; Health aspects; Herpes simplex; Herpes simplex virus; Herpes viruses; Herpesvirus 1, Human; Herpesvirus 3, Human; Human; Humans; Infections; Latency; Latent infection; Lymphocytes T; Peptides; Prevalence; Proteins; Proteome; Proteomes; Reverse transcription; Shingles (Disease); T cells; Trigeminal Ganglion; Varicella; Varicella-zoster virus; Viruses; Netherlands; Human; T-cells; Varicella-zoster virus; Trigeminal ganglion; Herpes simplex virus; Latency
• ISSN: 1742-2094; 1742-2094
• DOI: 10.1186/s12974-023-02820-y

Trigeminal ganglia (TG) neurons are an important site of lifelong latent varicella-zoster virus (VZV) infection. Although VZV-specific T-cells are considered pivotal to control virus reactivation, their protective role at the site of latency remains uncharacterized. Paired blood and TG specimens were obtained from ten latent VZV-infected adults, of which nine were co-infected with herpes simplex virus type 1 (HSV-1). Short-term TG-derived T-cell lines (TG-TCL), generated by mitogenic stimulation of TG-derived T-cells, were probed for HSV-1- and VZV-specific T-cells using flow cytometry. We also performed VZV proteome-wide screening of TG-TCL to determine the fine antigenic specificity of VZV reactive T-cells. Finally, the relationship between T-cells and latent HSV-1 and VZV infections in TG was analyzed by reverse transcription quantitative PCR (RT-qPCR) and in situ analysis for T-cell proteins and latent viral transcripts. VZV proteome-wide analysis of ten TG-TCL identified two VZV antigens recognized by CD8 T-cells in two separate subjects. The first was an HSV-1/VZV cross-reactive CD8 T-cell epitope, whereas the second TG harbored CD8 T-cells reactive with VZV specifically and not the homologous peptide in HSV-1. In silico analysis showed that HSV-1/VZV cross reactivity of TG-derived CD8 T-cells reactive with ten previously identified HSV-1 epitopes was unlikely, suggesting that HSV-1/VZV cross-reactive T-cells are not a common feature in dually infected TG. Finally, no association was detected between T-cell infiltration and VZV latency transcript abundance in TG by RT-qPCR or in situ analyses. The low presence of VZV- compared to HSV-1-specific CD8 T-cells in human TG suggests that VZV reactive CD8 T-cells play a limited role in maintaining VZV latency.