Overall, these data suggest that SVV infection in rhesus macaques recapitulates key features of VZV latency. == Physique 2. in the cytoplasm of neurons in latently infected monkey ganglia by immunohistochemistry. We also present the first in depth analysis of the immune response to SVV. Infected animals produced a strong humoral and cell-mediated immune response to SVV, as assessed by immunohistology, serology and flow cytometry. Intrabronchial inoculation of rhesus macaques with SVV provides a novel model to analyze viral and immunological mechanisms of VZV latency and reactivation. == Author Summary == Varicella zoster virus (VZV) is usually a ubiquitous herpesvirus that causes chickenpox (varicella) and establishes a life-long latent contamination in humans. VZV can then reactivate causing herpes zoster, commonly known as shingles, a painful Eugenol and debilitating disease that can be life-threatening in elderly and immunocompromised individuals. Our understanding of immunological factors that control VZV replication is limited due to the fact that VZV causes disease only in humans. Simian varicella virus (SVV) is usually a simian counterpart of VZV that infects nonhuman primates. Our study showed for the first time that contamination of rhesus macaques with SVV recapitulates key aspects of VZV contamination from chickenpox and the resolution of acute viremia to the establishment of latency in ganglia, and the development of B and T cell responses to virus. This model will allow us to improve our understanding of the immune response to varicella virus, and to develop and test vaccines and antiviral drugs that can reduce the incidence of shingles and its attendant neurological complications. == Introduction == Varicella zoster virus (VZV), a neurotropic alpha herpesvirus, is the etiological agent of varicella (chickenpox). VZV establishes latency in ganglia and can reactivate to produce herpes zoster (shingles), a debilitating disease for the elderly and immunocompromised. Studies of VZV pathogenesis have been hampered by the lack of an animal model that consistently recapitulates both the virological and immunological hallmarks of both acute and latent VZV contamination. Experimental inoculation of mice, rats and nonhuman primates (NHP) with VZV results in seroconversion but not varicella[1],[2],[3]. In weanling guinea pigs, seroconversion, viremia, an exanthem and animal-to-animal spread after VZV contamination have been found[4]. Although humoral and cellular immune responses have been briefly characterized in the guinea pig model, the scarcity of immunological tools specific for this species have precluded in depth analysis[5],[6]. Further, VZV does not reactivate in any of these Rabbit Polyclonal to MYT1 models. A SCID-humanized (SCID-hu) mouse model was developed in which co-implants of human fetal thymus/liver tissue were introduced under the kidney capsule. Fetal skin was then introduced subcutaneously as full thickness dermal grafts and later infected by injection of VZV-infected cells into the implanted tissue[7]. Further studies showed that the skin implants can also be infected and display hallmarks of VZV lesions following intravenous transfer of VZV infected tonsilar T cells[8]. Although this model contributed significantly to our understanding of VZV dissemination and pathogenesis, the chimeric and partially immunodeficient status of the Eugenol host coupled with the need for fetal liver, thymus, tonsils and skin, precluded in depth Eugenol studies of the role of the host immune response in the establishment and maintenance of VZV latency. Simian varicella virus (SVV) produces a naturally occurring exanthematous disease in NHP that mimics human varicella[9]. Both virus genomes have been sequenced and are colinear, sharing up to 75% DNA similarity[10],[11],[12]. Furthermore, SVV and VZV encode antigenically related polypeptides[13],[14],[15]. Like VZV, SVV becomes latent in ganglionic neurons[16],[17],[18],[19]and reactivates after environmental stress or immune suppression[9],[20],[21],[22]. However, although.