Studies on immune response to Human Immunodeficiency Virus-1 proteins using DNA immunization

Abstract

Human Immunodeficiency Virus-1 (HIV-1) infection is characterized by chronic immune activation and progressive loss of CD4+ T cells leading to a wide array of immune dysfunction particularly involving immune response directed against viral antigens. HIV-1 encodes for fifteen proteins for e.g. tat, rev, nef, gp120, gag etc, any of which might serve as a target for immune recognition. Immune response to the envelope proteins have been studied a lot due to their presence on the surface of the virus. The Tat protein has also been focus of immunization studies because of its potent regulatory activity. The Tat protein although being nuclear in localization, is also released from infected cells and acts on uninfected cells. Furthermore, a correlation between anti-Tat immune response and slow progression of the disease exists in the literature. Several investigators have used Tat as a potential candidate for vaccination with encouraging results Although Tat has been found to be a successful candidate; few reports imply that Tat acts as an immunosuppresor for the co-immunized viral antigens. The mechanism by which Tat mediates its immunosuppression remains to be elucidated. In order to identify unambiguously the role of Tat in immune response of a co-immunized antigen, we have constructed a bicistronic vector expressing Tat and gp120 from CMV promoter with an internal ribosome entry site and analyzed the role of Tat in elicitation of gp-120 specific immune response. The T cell responses to gp120 were greatly diminished in mice co-immunized with Tat as compared to mice immunized with gp120 alone. This immunosuppressive activity of Tat was not confined to viral antigen only as it also suppressed the immune response of an unrelated antigen. Analysis of cytokine profile suggests that Tat induces IL-10 and since IL-10 has been demonstrated to have appreciable T cell inhibitory activity, it is plausible that IL-10 could be responsible for Tat mediated immunosuppresion.