Open Access HIV and the Sharpen Edge Between Protective and Pathogenic Immune Responses to the CD4 Self Antigen

Abstract: The homeostasis of the immune function is severely impaired by HIV exposure, not only as an effect of the in-fection but also as a consequence of interactions of viral proteins with key elements of the immune system. In this context, in HIV infected individuals autoimmune responses to membrane CD4, the HIV receptor, are generally considered in-volved in the catastrophic loss of most part of the T helper lymphocytes. However, also in a portion of individuals natu-rally resistant to HIV-1 infection anti-CD4 antibodies appear, which are devoid of any harmful consequence and are asso-ciated to the lack of conventional signs of infection. Here, we will focus on the differences of these two oppositely polarized outcomes, with particular reference to the fine specificities of these antibodies in HIV infected versus naturally resistant individuals and to the role of partially or totally CD4-gp120 complex-specific antibodies. We will review evidence supporting the notion that the fine tuning of the anti-self immune response to the HIV-1 receptor may contribute to determine whether viral exposure will bring to infection or, alternatively, to protective immunity. The sharpen edge between harmful and protective self-reactivity appears as a key event in individuals naturally resistant to HIV infections with promising implications in the design innovative anti-HIV strategies