Genome-wide analysis of t cell responses during acute and latent simian varicella virus infections in rhesus macaques

Varicella zoster virus (VZV) is the etiological agent of varicella (chickenpox) and herpes zoster (HZ [shingles]). Clinical observa- tions suggest that VZV-specific T cell immunity plays a more critical role than humoral immunity in the prevention of VZV reac- tivation and development of herpes zoster. Although numerous studies have characterized T cell responses directed against se-lect VZV open reading frames (ORFs), a comprehensive analysis of the T cell response to the entire VZV genome has not yet been conducted. We have recently shown that intrabronchial inoculation of young rhesus macaques with simian varicella virus (SVV), a homolog of VZV, recapitulates the hallmarks of acute and latent VZV infection in humans. In this study, we character- ized the specificity of T cell responses during acute and latent SVV infection. Animals generated a robust and broad T cell re-sponse directed against both structural and nonstructural viral proteins during acute infection in bronchoalveolar lavage (BAL) fluid and peripheral blood. During latency, T cell responses were detected only in the BAL fluid and were lower and more re-stricted than those observed during acute infection. Interestingly, we identified a small set of ORFs that were immunogenic dur- ing both acute and latent infection in the BAL fluid. Given the close genome relatedness of SVV and VZV, our studies highlight immunogenic ORFs that may be further investigated as potential components of novel VZV vaccines that specifically boost T cell immunity.