DC-SIGN on B Lymphocytes Is Required For Transmission of HIV-1 to T Lymphocytes

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Abstract
Infection of T cells by HIV-1 can occur through binding of virus to dendritic cell (DC)-specific ICAM-3 grabbing nonintegrin (DC-SIGN) on dendritic cells and transfer of virus to CD4+ T cells. Here we show that a subset of B cells in the blood and tonsils of normal donors expressed DC-SIGN, and that this increased after stimulation in vitro with interleukin 4 and CD40 ligand, with enhanced expression of activation and co-stimulatory molecules CD23, CD58, CD80, and CD86, and CD22. The activated B cells captured and internalized X4 and R5 tropic strains of HIV-1, and mediated trans infection of T cells. Pretreatment of the B cells with anti–DC-SIGN monoclonal antibody blocked trans infection of T cells by both strains of HIV-1. These results indicate that DC-SIGN serves as a portal on B cells for HIV-1 infection of T cells in trans. Transmission of HIV-1 from B cells to T cells through this DC-SIGN pathway could be important in the pathogenesis of HIV-1 infection. A cell surface molecule, DC-SIGN, is known to bind the AIDS virus, human immunodeficiency virus 1 (HIV-1), on dendritic cells. HIV-1 can then be transferred from these dendritic cells to CD4+ T cells, in which the virus replicates and kills the T cells. Here, Rappocciolo and colleagues present their findings that DC-SIGN serves a similar function on a subset of B cells of the peripheral blood and tonsils. Although B cells that express DC-SIGN do not replicate HIV-1, they serve as portals for transfer and enhanced HIV-1 infection of CD4+ T cells, the major site of virus replication in the host. This newly described pathway for HIV-1 infection of T cells via B cells could be important in the pathogenesis of the virus infection.