dc-sign on b lymphocytes is required for transmission of hiv-1 to t lymphocytesdc-sign b淋巴细胞上所需的传播hiv - 1 t淋巴细胞.pdf

DC-SIGN on B Lymphocytes Is Required For Transmission of HIV-1 to T Lymphocytes 1* 1 1¤ 1 2 1 Giovanna Rappocciolo , Paolo Piazza , Craig L. Fuller , Todd A. Reinhart , Simon C. Watkins , David T. Rowe , Mariel Jais1, Phalguni Gupta1,3, Charles R. Rinaldo, Jr.1,3 1 Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America, 2 Department of Cell Biology and Physiology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America, 3 Department of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America 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 CD4þ 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. Citation: Rappocciolo G, Piazza P, Full