Varicella-zoster virus immune evasion

CD4(+) and CD8(+) T cells play dual roles in varicella-zoster virus (VZV) p athogenesis. The first role is to deliver the virus to cutaneous sites duri ng primary VZV infection, permitting replication at these sites and the suc cessful transmission of the virus to other susceptible individuals. The sec ond contribution of T cells is to provide the critical antigen-specific ada ptive 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 in fection and silent persistence in dorsal root ganglia. Interference with an tigen presentation by MHC class I downregulation may be expected to play a role in both circumstances. Transient interference with MHC class II expres sion in varicella skin lesions should facilitate local replication and tran smission. In addition, when VZV reactivates, the capacity of viral gene pro ducts to block the upregulation of MHC class II expression triggered by int erferon-gamma should permit a sufficient period of viral replication to cau se the lesions of herpes tester, despite the presence of VZV-specific T cel ls, and to allow transmission of the virus to susceptible individuals. Alth ough the effort is at an early stage compared to studies of other viral pat hogens, identifying the VZV gene products that exert these effects and thei r mechanisms of interference has the potential to reveal novel aspects of M HC class I and class II antigen processing and presentation.