Expression of the C-type lectin receptor CD205 on B cells mediates HIV-1 binding and trans infection of CD4 + T cells
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Antigen presenting cells (APC) can bind HIV-1 and subsequently trans infect CD4 + T cells. In comparison to direct ( cis ) infection of CD4 + T cells by free virus, APC-mediated HIV-1 trans infection is significantly more efficient and requires lower virus titers. As such, B cell-mediated HIV-1 trans infection of CD4 + T cells, particularly in secondary lymphoid organs (SLO) where B and CD4 + T cells interact frequently in and around B cell follicles, represents an efficient pathway for establishing and maintaining the latent HIV-1 reservoir. The molecular events involved in HIV-1 binding to B cells and transfer to CD4 + T cells are poorly understood. B cells are exposed to various activation signals in SLO including CD40 ligand (CD40L), interleukin-4 (IL-4), interferon-γ (IFN-γ), and B cell activating factor (BAFF). Here, we treated B cells with these different signals, or combination of signals, to identify those that facilitate HIV-1 binding to B cells and trans -infection of CD4 + T cells, and the mechanisms involved. We found that CD40L/IL-4 stimulated B cells are highly efficient mediators of HIV-1 trans infection of CD4 + T cells due to their enhanced capacity to bind HIV-1. Single cell RNA sequencing of differentially stimulated B cell populations revealed that CD40L/IL-4 stimulation significantly induced expression of the C-type lectin CD205. Confocal microscopy revealed that HIV-1 and CD205 co-localized on CD40L/IL-4 stimulated B cells, and antibody blocking of CD205 on these cells significantly reduced HIV-1 binding. Taken together, this study identifies CD205 as a critical receptor on B cells that facilitates HIV-1 binding and the transfer of virus to CD4 + T cells. Insight into the role of B cell mediated HIV-1 trans infection of CD4 + T cells is critical to optimizing the effectiveness of HIV-1 therapies in SLO.
Author summary
HIV-1 spreads in part by exploiting antigen presenting cells such as B cells, which bind and transfer virus to CD4 + T cells through a process called trans infection. The molecular events involved in HIV-1 binding to B cells and transfer to CD4 + T cells are undefined. B cells frequently interact with CD4 + T cells within B cell follicles in secondary lymphoid organs (SLO), which represent a major reservoir of HIV-1. Here, we treated B cells with different SLO-specific activation signals to identify those that facilitate B cell-mediated trans infection of CD4 + T cells, and the mechanisms involved. We found that B cells stimulated with CD40 ligand (CD40L) and interleukin-4 (IL-4) become highly efficient mediators of trans infection due to their increased ability to bind HIV-1. This enhanced binding is driven by upregulation of the C-type lectin receptor CD205, which acts as a critical receptor that facilitates HIV-1 binding and trans infection of CD4 + T cells. These findings may inform strategies for limiting the viral reservoir in people living with HIV.
