Consequences of dendritic cell (DC)-immunodeficiency virus interactions: chemically inactivated virus as a model for...

We have established a model approach to study DC-virus communication, in which classically immature and mature DCs can be compared. The striking observation that macropinocytically poor mature DCs capture and then internalize whole virus particles has substantial implications for both antigen processing and presentation as well as cell to cell transmission of virus from DCs to nearby T cells (as well as other cell types). Studies are ongoing using this system to determine what molecules and mechanisms are involved in virus binding and internalization by immature versus mature DCs. Discerning the consequences of the differential fates of virus in immature versus mature monocyte-derived DCs should provide important information on how virus captured by DCs is processed for immune activation versus virus dissemination. While there are many features shared by monocyte-derived DCs and DCs directly isolated from blood or tissues, there are some important distinctions between these DC subsets and their activation stage. These traits have considerable influence on immune activation by DCs as well as how the individual DC subset handles an immunodeficiency virus. Thus, this approach is ultimately being applied to specific DC subsets, especially those found at the body surfaces where the first DC-virus interactions most frequently occur in vivo. Utilizing this system, we hope to better comprehend the initial events of DC-virus communication to (i) facilitate the development of strategies to block these events and prevent the onset of infection and (ii) identify how to augment the generation of broad anti-viral immunity.