T cell responses against structural proteins develop rapidly during acute simian varicella virus infection and are maintained during viral latency (P6133)

Abstract Varicella zoster virus (VZV) is the etiological agent of varicella and herpes zoster. Clinical observations suggest that successful control of VZV during both primary infection and reactivation is mediated by cellular rather than humoral immunity. Numerous studies have characterized T cell responses directed against select VZV open reading frames (ORF), but a comprehensive analysis of the T cell response to the entire VZV genome has not yet been conducted. We have 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 characterized the specificity of T cell responses during acute and latent SVV infection. We identified several SVV ORFs targeted by T cell responses in majority of animals examined during both acute and latent infection. We show that structural proteins are targeted by both CD4 and CD8 T cells, and immediate early/early viral proteins are primarily targeted by CD8 T cells. Also, while both CD4 and CD8 T cell responses are detected during acute SVV infection, latent infection elicits primarily CD8 T cell responses. These results suggest that CD4 T cell immunity may wane faster than CD8 T cell immunity. Given the close genome relatedness of SVV and VZV, our studies highlight immunogenic ORFs to be further investigated as potential components of second-generation VZV vaccines designed to boost T cell immunity.