It was previously demonstrated that VZV encodes two separate immune evasion strategies of specifically downregulating cell surface MHC class I (3) and inhibiting the upregulation of gamma interferon-induced MHC class II expression (2) during productive contamination of primary HFFs

It was previously demonstrated that VZV encodes two separate immune evasion strategies of specifically downregulating cell surface MHC class I (3) and inhibiting the upregulation of gamma interferon-induced MHC class II expression (2) during productive contamination of primary HFFs. of CD83 in cytoplasmic vesicles. Importantly, VZV contamination of mature DCs significantly reduced their ability to stimulate the proliferation of allogeneic T lymphocytes. Fabomotizole hydrochloride These data demonstrate that mature DCs are permissive for VZV and that infection of these cells reduces their ability to function Fabomotizole hydrochloride properly. Thus, VZV has evolved yet another immune evasion strategy that would likely impair immunosurveillance and enhance the chances for lifelong persistence in the human population. Varicella-zoster virus (VZV) is a highly species-specific herpesvirus that infects up to 90% of the human population (6). During primary infection, VZV is responsible for the predominantly childhood disease varicella (chicken pox). Following resolution of primary infection by the host immune system, the virus establishes a lifelong, latent contamination in the dorsal root ganglia of the host. Reactivation from this site may occur many years later, resulting in herpes zoster (shingles), a condition which can be complicated by prolonged pain associated with postherpetic neuralgia (6,37). The induction of VZV-specific T-cell immunity is critical for Fabomotizole hydrochloride host recovery from varicella, and both major histocompatibility complex (MHC) class I-restricted CD8+T lymphocytes and MHC class II-restricted CD4+T lymphocytes are sensitized to viral antigens during primary contamination (5). The role of VZV-specific T lymphocytes in maintaining the equilibrium between the host and virus during latency is usually implied by the association between a decline in the frequency of circulating VZV-specific Nrp2 T lymphocytes and an increased risk of VZV reactivation, causing herpes zoster (26). However, like several other herpesviruses, VZV has the capacity to interfere with the expression of MHC class I and MHC class II molecules (2,3). VZV-encoded immunomodulatory mechanisms that limit the presentation of VZV peptides by MHC class I or MHC class II pathways to effector T lymphocytes are likely to play an important role in the pathogenesis of VZV disease and persistence of the virus in the human population (1). Several human viruses have evolved alternative strategies of evading immune recognition by selectively infecting and altering the function of specialized immune cells involved in host immune surveillance. For example, T lymphocytes play a critical role in adaptive immunity, and viruses such as human immunodeficiency virus (HIV) and measles virus can infect and destroy these cells, which may result in significant immunosuppression of the host (7,16,17). Dendritic cells (DCs) are potent antigen-presenting cells critical for the initiation of a successful antiviral immune response through the stimulation of immunologically nave T lymphocytes (8,34). DCs located in the periphery exist as immature cells, expressing low levels of MHC class I and MHC class II molecules and costimulatory molecules such as CD80 and CD86. Immature DCs readily take up antigen and are induced to migrate to the secondary lymphoid organs, where they undergo maturation and present processed antigens to antigen-specific T lymphocytes (8,34,35). Maturation of DCs results in the downregulation of antigen uptake and processing properties and the upregulation of MHC class I and MHC class II molecules; increased surface expression of costimulatory molecules CD80, CD86, and CD40 and the maturation molecule CD83; and upregulation of adhesion molecules such as ICAM-1 (CD54) (8,14,36,39-42). The ability of mature DCs to efficiently activate nave T lymphocytes which subsequently eliminate target cells (e.g., virus-infected cells) has been attributed to their expression of these specific cell surface immune molecules (11). It has been postulated elsewhere that DCs would be an ideal target for viruses seeking to evade or delay the immune response by disrupting their function (11). In this respect, viruses including herpes simplex virus type 1 (HSV-1) (23), human cytomegalovirus (29), human herpesvirus 6 (20), measles.