DCs are, potentially, one of the important cell types in the early transmission of HIV-1 to CD4+ T cells. The cellular and viral factors that affect the process of early-stage HIV-1 transmission have been extensively studied and characterized. Many cell surface molecules affect DC-mediated HIV-1 transmission to CD4+ T cells, but none of these molecules appear to be exclusively responsible for differential transmission between different DC subsets. For example, both DC-SIGN-dependent and independent transmission can occur in DCs.
HIV-1 exploits normal DC cellular process, such as macropinocytosis, and natural interactions with CD4+ T cells, such as ICAM-1 binding to LFA-1, to promote viral infection and cell-to-cell transmission. HIV-1 expresses proteins which promote the process of DC-mediated HIV-1 transmission to CD4+ T cells. In particular, the multifunctional pathogenic accessory protein Nef plays a key role in promoting DC-mediated HIV-1 transmission to CD4+ T cells by activating CD4+ T cells and modulating DC interactions with T cells. Overall, the cellular and viral factors that promote DC-mediated HIV-1 transmission to CD4+ T cells ensure efficient HIV-1 transmission and spread within the host and establishment of long-term infection.
Future work will involve further characterizations of cellular and viral factors that regulate DC-mediated HIV-1 transmission to CD4+ T cells, particularly those that act specifically in different DC subsets. A major area of study is the characterization of the physical interaction that occurs at the VS that promotes DC-mediated HIV-1 transmission to CD4+ T cells, for example, how CD4+ T cells efficiently retrieve HIV-1 from the deep invagination on the DC cell surface. These studies will help to better understand the mechanisms underlying HIV-1 cell-to-cell transmission.
Cellular and viral factors that affect DC-mediated transmission of HIV-1 to CD4+ T cells are also, potentially, important targets for therapeutic strategies, such as drugs that specifically target the interactions that promote formation of the VS and/ or strategies to target the HIV-1 pool associated with DCs. Drugs that target the initial interactions that occur between HIV-1 and DCs have the potential as topical treatments at the mucosal surfaces to prevent the initial DC-mediated HIV-1 transmission events that lead to establishment of persistent infection.