Detection of SVV antigen in multiple tissues upon CD4 T cell depletion and virus reactivation suggests a critical role for CD4 T cell immunity in controlling varicella virus latency. IMPORTANCE Reactivation of latent VZV Celiprolol HCl in Celiprolol HCl humans can result in serious neurological complications. after 7?days in the monkey with the most extensive CD4 T cell depletion (5%) and in all other monkeys at 10 to 49?days posttreatment, with recurrent zoster in one treated monkey. SVV DNA was detected in the lung from two of five monkeys, in bronchial lymph nodes from one of the five monkeys, and in ganglia from at least two dermatomes in three of five monkeys. Immunofluorescence analysis of skin rash, lungs, lymph nodes, and ganglia revealed SVV ORF63 protein at the following sites: sweat glands in skin; type II cells in lung alveoli, macrophages, and dendritic cells in lymph nodes; and the neuronal cytoplasm of ganglia. Detection of SVV antigen in multiple tissues upon CD4 T cell depletion and virus reactivation suggests a critical role for CD4 T cell immunity in controlling varicella virus latency. IMPORTANCE Reactivation of latent VZV in humans can result in serious neurological complications. VZV-specific cell-mediated immunity is critical for the maintenance of latency. Similar to VZV in humans, SVV causes varicella in monkeys, establishes ZAP70 latency in ganglia, and reactivates to produce shingles. Here, we show that depletion of CD4 T cells in rhesus macaques results in SVV reactivation, with virus antigens found in zoster rash and SVV DNA and antigens found in lungs, lymph nodes, and ganglia. These results suggest the critical role of CD4 T cell immunity in controlling varicella virus latency. model of varicella-zoster virus latent infection of dorsal root ganglia. J Neurosci Res 26:83C89. doi:10.1002/jnr.490260110. [PubMed] [CrossRef] [Google Scholar] 18. Lowry PW, Sabella C, Koropchak CM, Watson BN, Thackray HM, Abbruzzi GM, Arvin AM. 1993. Investigation of the pathogenesis of varicella-zoster virus infection in guinea pigs by using polymerase chain reaction. J Infect Dis 167:78C83. doi:10.1093/infdis/167.1.78. [PubMed] [CrossRef] [Google Scholar] 19. Chen JJ, Gershon AA, Li ZS, Lungu O, Gershon MD. 2003. Latent and lytic infection of isolated guinea pig enteric ganglia by varicella-zoster virus. J Med Virol 70(Suppl 1):S71CS78. doi:10.1002/jmv.10325. [PubMed] [CrossRef] [Google Scholar] 20. Debrus S, Sadzot-Delvaux C, Nikkels AF, Piette J, Rentier B. 1995. Varicella-zoster virus gene 63 encodes an immediate-early protein that is abundantly expressed during latency. J Virol 69:3240C3245. [PMC free article] [PubMed] [Google Scholar] 21. Kennedy PG, Grinfeld E, Bontems S, Sadzot-Delvaux C. 2001. Varicella-zoster virus gene expression in latently Celiprolol HCl infected rat dorsal root ganglia. Virology Celiprolol HCl 289:218C223. doi:10.1006/viro.2001.1173. [PubMed] [CrossRef] [Google Scholar] 22. Willer DO, Ambagala AP, Pilon R, Chan JK, Fournier J, Brooks J, Sandstrom P, Macdonald DS. 2012. Experimental infection of cynomolgus macaques (does not affect virus load in macaque elite controllers. J Virol 85:7454C7459. doi:10.1128/JVI.00738-11. [PMC free article] [PubMed] [CrossRef] [Google Scholar] 44. Pahar B, Cantu MA, Zhao W, Kuroda MJ, Veazey RS, Montefiori DC, Clements JD, Aye PP, Lackner AA, Lovgren-Bengtsson K, Sestak K. 2006. Single epitope mucosal vaccine delivered via immunostimulating complexes induces low level of immunity against simian-HIV. Vaccine 24:6839C6849. doi:10.1016/j.vaccine.2006.06.050. [PubMed] [CrossRef] [Google Scholar] 45. Traina-Dorge V, Pahar B, Marx P, Kissinger P, Montefiori D, Ou Y, Gray WL. 2010. Recombinant varicella vaccines induce neutralizing antibodies and cellular immune responses to SIV and reduce viral loads in immunized rhesus macaques. Vaccine 28:6483C6490. doi:10.1016/j.vaccine.2010.07.018. [PMC free article] [PubMed] [CrossRef] [Google Scholar] 46. Soike KF, Huang JL, Zhang JY, Bohm R, Hitchcock MJ, Martin JC. 1991. Evaluation of infrequent dosing regimens with ( em S /em )-1-[3-hydroxy-2-(phosphonylmethoxy) propyl]-cytosine ( em S /em -HPMPC) on simian varicella infection in monkeys. Antiviral Res 16:17C28. doi:10.1016/0166-3542(91)90055-V. [PubMed] [CrossRef] [Google Scholar].