Grant: Project Grant

A vaccine against HIV is crucially required worldwide to limit the spread of this virus. The major HIV-infected (HIV+) cell population, a type of white blood cells known as CD4 T cells, comes in multiple different "flavours", each with different functions. In order to develop a vaccine that can teach the immune system how to target and kill HIV+ cells, scientists must first understand which flavors of CD4 T cells are infected. However, currently available technologies have made it difficult to visualize these HIV+ cells in great detail. Previous work has relied on looking at the relative numbers of HIV+ cells in different populations, rather than the individual HIV+ cells, or studying HIV infection using cells and viruses grown in the lab. The interactions between these "in vitro" cells and viruses may be very different to the events occurring within a HIV-positive individual. To address this important issue, we have developed a novel assay that, for the first time, allows very rare HIV+ cells to be visualized at a single-cell level. We will perform in-depth analysis of individual HIV+ cells from the blood of patients who are infected with HIV. We will also use an animal model of HIV, SIV in non-human primates (monkeys), to image the infected cells in important tissues and organs. This will provide researchers with a highly detailed picture of HIV+ cells and guide development of a vaccine. In addition to a vaccine, a cure is required to treat those individuals that are HIV-positive. Antiretroviral therapy (ART) is not a cure for HIV; as long as a patient takes their medication the virus is forced into hiding, but it can reappear when ART is stopped. Specialized drugs (known as latency reversing agents or LRAs) have been developed to kick the virus out of its hiding place. We will investigate how different flavors of CD4 T cells respond to LRAs, and use this knowledge to inform studies working towards a cure for HIV.