Modulation of the immunological synapse: a key to HIV-1 pathogenesis?

The success and pathogenicity of HIV-1 largely resides in the function of the viral protein Nef. Here, the authors propose that Nef modulates a T cell's ability to form an immunological synapse and modulates T-cell activation to favour viral replication and spread. AIDS is the result of a constant struggle between the lentivirus HIV and the immune system. Infection with HIV interferes directly with the function of CD4 + T cells and manipulates the host immune response to the virus. Recent studies indicate that the viral protein Nef, a central player in HIV pathogenesis, impairs the ability of infected lymphocytes to form immunological synapses with antigen-presenting cells and affects T-cell-receptor-mediated stimulation. An integrative picture of the abnormal behaviour of HIV-infected lymphocytes is therefore emerging. We propose that modulating lymphocyte signalling, apoptosis and intracellular trafficking ensures efficient spread of the virus in the hostile environment of the immune system.