DC-SIGN on B lymphocytes is required for transmission of HIV-1 to T lymphocytes.
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.
Rappocciolo
Giovanna
G
Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. giovanna@pitt.edu
Piazza
Paolo
P
Fuller
Craig L
CL
Reinhart
Todd A
TA
Watkins
Simon C
SC
Rowe
David T
DT
Jais
Mariel
M
Gupta
Phalguni
P
Rinaldo
Charles R
CR
D000163:Acquired Immunodeficiency Syndrome / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D015703:Antigens, CD / Q000032:analysis; D001402:B-Lymphocytes / Q000737:chemistry* / Q000187:drug effects / Q000473:pathology / Q000821:virology; D001773:Blood Cells / Q000737:chemistry / Q000473:pathology / Q000821:virology; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000502:physiology / Q000821:virology*; D023201:CD40 Ligand / Q000494:pharmacology; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D015658:HIV Infections / Q000276:immunology* / Q000503:physiopathology; D015497:HIV-1 / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000502:physiology; D014066:Palatine Tonsil / Q000737:chemistry / Q000473:pathology / Q000821:virology; D011485:Protein Binding; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*
D015703:Antigens, CD; C433029:CLEC4M protein, human; D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D023201:CD40 Ligand; D015847:Interleukin-4