Latent HIV genes can be 'smoked out' of human cells. The so-called 'shock and kill' technique, described in a preclinical study in BioMed Central's open access journal Retrovirology, might represent a new milestone along the way to the discovery of a cure for HIV/AIDS.
Dr. Enrico Garaci, president of the Istituto Superiore di Sanit (the Italian Institute of Health) and Dr. Andrea Savarino, a retrovirologist working at the institution, worked with a team of researchers to study the so-called "barrier of latency" which has been the main obstacle to HIV eradication from the body.
Cells harbouring a quiescent HIV genome are responsible for HIV persistence during therapy. In other words, HIV-1 genes become pieces of the human organism, and many scientists have simply thought there is nothing we can do. Dr Savarino's team aimed to 'smoke out' the virus in order to render the latently infected cells targetable by the immune system or artificial means. They write, "This can be achieved using inhibitors of histone deacetylases (HDACs), which are a class of enzymes that maintain HIV latency. However, their effects on HIV are evident only when used in toxic quantities".
To overcome this problem, the Italian researchers tested a collection of HDAC inhibitors, some of which specifically target only certain enzyme isoforms (class I HDACs) that are involved in HIV latency. The toxicity of this approach, however, was not markedly decreased, although it compromises a more limited number of cellular pathways. Moreover, at non-toxic quantities, class I HDAC inhibitors were able to induce the 'awakening' of a portion of cells within a latently infected cell population. The researchers then repeated the experiment adding a drug inducing oxidative stress, buthionine sulfoximine (BSO). The results showed that BSO recruited cells non-responsive to the HDAC inhibitors into the responding cell population. An important result was that the infected cell
|Contact: Graeme Baldwin|