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.
Highlights
human immunodeficiency virus 1 (HIV-1) can bind to the type II C-type lectin receptor, dendritic cell (DC)-specific ICAM-3 grabbing nonintegrin (DC-SIGN; CD209), on myeloid DC and be transferred to CD4þ T cells [1,2]
B cells that express DC-specific ICAM-3 grabbing nonintegrin (DC-SIGN) do not replicate HIV-1, they serve as portals for transfer and enhanced HIV-1 infection of CD4þ T cells, the major site of virus replication in the host
To further delineate the relationship of B cell activation to DC-SIGN, we examined whether stimulation of B cells with the T helper type 2 (Th2) cytokine interleukin 4 (IL-4) alone or in combination with the CD4þ T cell activation factor CD40 ligand (CD40L) could alter expression of DC-SIGN and CD23, a procedure that mimics activation of B cells by CD4þ T helper cells during antigen processing [18,19]
Summary
HIV-1 can bind to the type II C-type lectin receptor, dendritic cell (DC)-specific ICAM-3 grabbing nonintegrin (DC-SIGN; CD209), on myeloid DC and be transferred to CD4þ T cells [1,2]. An important feature of this trans pathway is that the virus does not establish an efficient, productive infection in these DC. Rather, it is captured by the DC and internalized in distinct intracellular compartments, and transmitted to CD4þ T cells wherein it undergoes productive replication [3]. It is captured by the DC and internalized in distinct intracellular compartments, and transmitted to CD4þ T cells wherein it undergoes productive replication [3] This is considered to be an alternative pathway to HIV-1 cis infection of T cells, macrophages, and DC that occurs through binding to the primary CD4 receptor and either of the chemokine coreceptors CXCR4 or CCR5. Other reports have proposed a role for B cells in HIV-1 infection involving B cell activation processes induced by nef-expressing macrophages [11]
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