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Session 15 Oral Abstract Session Neuropathogenesis Session Time: Tuesday, 10 am - 12:30 pm Room 606-609

10:30   63. Expression of DC-SIGN in Cultured Microglia and in the CNS of Individuals with and without HIV Dementia (HIV-D) L. Shawver1, F. Baribaud1, R. W. Doms1, C. Pardo-Villamizar2, J. McArthur2, and F. González-Scarano1* 1Univ. of Pennsylvania, Philadelphia and 2Johns Hopkins Univ., Baltimore, MD Background: DC-SIGN, a type II membrane protein, contains a C-type lectin domain that binds HIV strains of both X4 and R5 phenotypes, and has been implicated in the entry of HIV into dendritic cells, which can then transport the virus into lymph nodes and transfer it to other susceptible cells such as CD4+ lymphocytes. DC-SIGNR, a closely related molecule is present in endothelial cells. Both molecules may play a role in the tropism of HIV isolates by enhancing interactions at the cell surface in some cell types. Methods: Microglial cells were cultured from tissue obtained at the time of temporal lobectomy using methods previously described. CNS tissues from individuals with and without dementia classified using established clinical and neuropathological criteria were obtained from archival material. Expression of DC-SIGN or DC-SIGNR was determined by immunohistochemical staining with monoclonal antibodies generated against either or both molecules. Identification of the expressing cells as macrophages/microglia used peroxidase labeled lectin from Ricinus communis agglutinin (RCA-1). Results: DC-SIGN was easily identified on the cell surface of cultured microglia. DC-SIGN was also present throughout the CNS in both normal brain and in HIV-D cases. Expression was concentrated around the perivascular region, particularly in cases with prominent cellular infiltration. However, there was clear expression in small cells throughout the brain parenchyma, most of which were identified as belonging to the macrophage/microglia lineage by their reaction with RCA-1. Occasional multinucleated giant cells, the hallmark neuropathological finding in HIV infection of the CNS, were identified in some of these sections; they stained with the anti-DC-SIGN antibodies. Conclusions: DC-SIGN is expressed in microglial cells in vitro, and in perivascular macrophages and microglial cells in vivo. The role of this molecule in HIV infection in these cells is still unknown, but it is likely that it promotes efficient binding at the cell surface and possibly enhanced entry. Blocking studies designed to determine this are in progress.

©2002 9th Conference on Retroviruses and Opportunistic Infections