Simian varicella virus (SVV) infection of non-human primates models human varicella zoster virus (VZV) infection. Assessment of cell signaling immune responses in monkeys after primary SVV infection, after immunosuppression and during reactivation revealed strong pro-inflammatory responses and lesser anti-inflammatory components during varicella and reactivation. Pro-inflammatory mediators elevated during varicella included interferon-gamma (IFN-γ), interleukin (IL)-6, monocyte chemoattractant protein (MCP-1), interferon inducible T-cell α chemoattractant protein (I-TAC), interferon processing protein (IP-10), and anti-inflammatory interleukin-1 Receptor antagonist (IL-1Ra). After immunosuppression and at reactivation, levels of pro-inflammatory mediators MCP-1, eotaxin, IL-6, IL-8, MIF, RANTES (regulated-on-activation normal T-cell expressed and secreted), and HGF (hepatocyte growth factor) were elevated, as was the anti-inflammatory mediator IL-1Ra. Characterization of cytokine, chemokine and growth factor responses during different stages of varicella virus infection will facilitate immunotherapeutic and vaccine strategies.