Since 1986 our group has been studying interactions of HIV with dendritic cells and macrophages. These cells are two of the three key target cells for HIV, especially dendritic cells in the ano-genital mucosa and macrophages as viral reservoirs in brain. In the past we have defined how HIV traffics through and/or infects these cells, including the HIV interactions with their surface receptors and how it alters their biological functions to enhance viral spread. In macrophages HIV replicates at lower levels than T cells and does not kill the cells, thus providing a persistently infected reservoir in most tissues of the body but particularly in brain. HIV transmitted from dendritic cells to T cells in two different ways: via vesicles and by true infection. Our recent studies have shown how HIV alters the maturation status of dendritic cells and their ability to adhere to T cells, resulting in accelerated transfer of virus to the T cells. Most recently we have shown how HIV disturbs the protective interferon system in both cell types. Our current studies are aimed at determining exactly how HIV inhibits the interferon system, the host protective counter measures and how the virus is transferred to T cells resulting in either productive and latent infection (in collaboration with the Palmer and Harman groups).
We have also recently demonstrated that the surface molecule langerin on Langerhans cells plays a key role in transfer of HIV to T cells. Therefore we are developing inhibitors of this interaction as potential antiviral agents.
These studies are highly relevant to the development of topical prevention of ano-genital HIV infection via “microbicides” and also the development of vaccines, especially mucosal vaccines. These studies will be extended to epithelial dendritic cells in collaboration with the Harman group in the near future.