Varicella-zoster virus immune evasion.

CD4+ and CD8+ T cells play dual roles in varicella-zoster virus (VZV) pathogenesis. The first role is to deliver the virus to cutaneous sites during primary VZV infection, permitting replication at these sites and the successful transmission of the virus to other susceptible individuals. The second contribution of T cells is to provide the critical antigen-specific adaptive immunity needed to stop viral replication and maintain VZV latency in sensory ganglia. The equilibrium between VZV and the host can be predicted to be served by immune evasion mechanisms in at least two important ways, including the facilitation of cell-associated viremia during primary VZV infection and silent persistence in dorsal root ganglia. Interference with antigen presentation by MHC class I downregulation may be expected to play a role in both circumstances. Transient interference with MHC class II expression in varicella skin lesions should facilitate local replication and transmission. In addition, when VZV reactivates, the capacity of viral gene products to block the upregulation of MHC class II expression triggered by interferon-gamma should permit a sufficient period of viral replication to cause the lesions of herpes zoster, despite the presence of VZV-specific T cells, and to allow transmission of the virus to susceptible individuals. Although the effort is at an early stage compared to studies of other viral pathogens, identifying the VZV gene products that exert these effects and their mechanisms of interference has the potential to reveal novel aspects of MHC class I and class II antigen processing and presentation.