ECDO Honorary Lecture L-5 HIV-induced Cell Death: a Viral Strategy of Immune Evasion

Viruses have evolved numerous mechanisms to evade the host immune system, and one of the strategies developed by HIV is to activate apoptotic programs in order to destroy immune effectors. Not only does the HIV genome encode for proapoptotic proteins, which kill both infected and uninfected lymphocytes, but it also creates a state of chronic immune activation responsible for the exacerbation of physiological mechanisms of clonal deletion. HIV infects cells of the immune system and HIV-infection is characterized by the gradual loss of CD4+ T cells and a progressive immune deficiency that leads to opportunistic infections, and ultimately death. Although our understanding of CD4 T cell homeostasis is still incomplete and controversial, a growing body of evidence points to HIV-driven lymphocyte apoptosis as an important contributor to the destruction of the immune system Because of persistent expression of viral particles, this infection results in high turnover rates of T cells, leading to increased T cell proliferation that is physiologically controlled by increased apoptosis. In addition, HIV has developed strategies to trigger the apoptotic machinery in both infected and non-infected cells, inducing the destruction of the effectors of the immune system. Death receptors, such as CD95, TNF-RI and –II or the TRAIL system