Under conditions of naturally acquired primary varicella-zoster virus (VZV) infection, the first response of the naive host is mediated by the innate immune system through antiviral cytokines and the activation of NK cells [1]. These responses are likely to be important for the initial control of VZV at mucosal sites of inoculation and to trigger the induction and amplification of adaptive, VZV-specific immunity. NK cells can lyse VZV-infected targets [2], and activated NK cells are a major source of interferon (IFN)–g production, which enhances the clonal expansion of antigen-specific T cells. IFN-a inhibits VZV replication in vitro, and treatment with exogenous type I IFN-a reduced the severity of varicella in immunocompromised children with varicella [3]. In addition, VZV replication in skin is associated with extensive production of IFN-a by adjacent uninfected epidermal cells in the SCIDhu model of VZV pathogenesis; blocking this IFN-a response caused a dramatic increase in VZV spread in skin [4]. Innate mechanisms of immune control have the capacity to maintain the host-virus equilibrium, despite the VZV immune evasion strategies that inhibit both class I and class II major histocompatibility complex (MHC) mechanisms for antigen presentation to T cells while the virus is being transferred to skin and in early stages of cutaneous infection [4–6]. These strategies