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The identification of the cellular localization of DC-SIGN following interaction with HIV and other ligands

Objective

Dendritic cell specific intercellular adhesion molecule 3 grabbing non-integrin (DC-SIGN, CD209), a C-type lectin on the surface of immature monocyte derived dendritic cells, plays a key role in the transmission of human immunodeficiency virus (HIV) from d endritic cells to T cells. DC-SIGN captures HIV in vitro and transmits it very efficiently to target cells. This can be mimicked in a cell culture model using B-cell lines ectopically expressing DC-SIGN; we have found that only a very limited number of cell types are able to transmit virus. The mechanism of capture/transmission is largely unknown. We are especially interested in the role that internalization of the DC-SIGN/virus complex plays for transmission. This is very difficult to assess in dendritic c ells due to their complex nature. Our cell culture model provides the tools to answer this question. Comparison of cell types that are or are not capable to transmit DC-SIGN associated virus will provide insight into the role internalization plays. Using biochemical and microscopical means we want to identify subcellular localization of DC-SIGN in the different cell systems in response to challenge with virus and/or biological binding partners, such as intercellular adhesion molecules, or mannan. Knowledge about this mechanism would be needed if this early interaction of HIV with dendritic cells in the mucosal tissue should be tackled for an antiretroviral intervention strategy. Interruption of this interaction would provide a possibility for preventive measures against HIV/AIDS.

Call for proposal

FP6-2004-MOBILITY-12
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Funding Scheme

IRG - Marie Curie actions-International re-integration grants

Coordinator

FRAUNHOFER GESELLSCHAFT - FRAUNHOFER INSTITUT FUER ZELLTHERAPIE UND IMMUNOLOGIE