Immunology: Bringing HIV out of hiding

Two methods to reverse HIV latency, which may improve the chances of eliminating the virus, are described in animal studies published this week in Nature.

Current antiretroviral therapies are unable to completely clear HIV infection as the virus can ‘hide’ from the immune system in a latent form in cells. The eradication of HIV infection after prolonged viral suppression therapy has long been the focus of intense research. According to the ‘shock and kill’ method, the virus needs to be flushed out of latently infected cells and then eliminated. To date, efforts to ‘shock’ the virus out of hiding have not been successful or efficient.

Two studies demonstrate different methods to achieve robust virus reactivation of SIV in macaques and HIV in humanized mice. Guido Silvestri and colleagues use a combined approach that activates interleukin-15 (a signalling molecule essential for immune responses) and depletes CD8⁺ lymphocytes (immune cells that are thought to suppress viral transcription) to achieve substantial and persistent virus reactivation in all treated animals. Victor Garcia and colleagues use a drug that activates the NF-kappaB signalling pathway, a trigger of HIV gene expression that could make the virus more susceptible to elimination.

Although both of these shock approaches need to be combined with a kill component to achieve clearance of the reactivated virus, they constitute the most potent latency reversal approaches demonstrated to date and provide insights into the mechanisms responsible for the maintenance of viral latency.