Figure 3. HIV and the nucleolus – a potential therapeutic strategy?

Our knowledge of the interaction between HIV and the nucleolus is leading to the design of novel therapeutic strategies, and has been pioneered by John Rossi's group. Although these approaches are currently targeted at patients with both AIDS and lymphoma they might be applicable to all individuals infected with HIV-1. Haematopoietic stem cells are taken from infected individuals and treated with lentiviral vectors that contain an anti-tat/rev short hairpin RNA (shRNA), an anti-CCR5 ribozyme and a nucleolar-localizing trans-activation response element (TAR) RNA decoy. TAR is a region of secondary RNA structure that is located within the HIV long terminal repeat and is present in all HIV mRNAs. The region prevents the efficient use of the mRNA unless it is bound by the HIV transactivator (Tat) protein. The engineered stem cells then form part of a bone marrow transplant back into the (now) irradiated individual. As a result T cells are produced that are resistant to HIV-1 infection. As with anti-HIV chemotherapy, the triple combination approach is used to prevent the build up of resistant viruses.