Humoral and Cellular Immunity to Varicella‐Zoster Virus: An Overview

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