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Dendritic cells (DCs) are considered to be the main target cells for HIV-1 infection, and several DC-specific receptors have been implicated in the uptake of virus particles by DCs. The aim of this study was to verify the role of DC-SIGNR (DC-SIGNR, CLEC4G) in the internalization of HIV-1. To investigate this question, we used the HeLa-DC-SIGNR(+) cell line, which was previously developed in our laboratory and which stably expresses a truncated DC-SIGNR receptor. These cells express DC-SIGNR on the cell surface and internalize efficiently HIV-1. However, expression of DC-SIGNR in HeLa cells was not sufficient to mediate the uptake of HIV-1, suggesting that additional receptors or molecules are involved in this process. Using reverse transcription-PCR analysis, we found that DC-SIGNR was expressed in DCs and in a variety of epithelial cell lines, including HeLa cells, suggesting that DC-SIGNR is physiologically expressed on other cell types than just on DCs. In accordance with this, antibody internalization assays using a Fc-fusion receptor protein, known to interact with DC-SIGNR, showed that this protein is also expressed on other cell types. Competition with anti-DC-SIGNR antibodies confirmed that the uptake of HIV-1 by DC-SIGNR(+) cells is mediated by this receptor. We therefore conclude that DC-SIGNR is also expressed on other cells than
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