Dendritic Cell-Mediated trans-Enhancement of Human Immunodeficiency Virus Type 1 Infectivity Is Independent of DC-SIGN

Molecular Pathogenesis Program, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, 540 First Avenue, New York, NY 10016, USA.
Journal of Virology (Impact Factor: 4.44). 04/2007; 81(5):2519-23. DOI: 10.1128/JVI.01661-06
Source: PubMed


Dendritic cells (DCs) enhance human immunodeficiency virus type 1 (HIV-1) infection of CD4+ T lymphocytes in trans. The C-type lectin DC-SIGN, expressed on DCs, binds to the HIV-1 envelope glycoprotein gp120 and confers upon some cell lines
the capacity to enhance trans-infection. Using a short hairpin RNA approach, we demonstrate that DC-SIGN is not required for efficient trans-enhancement by DCs. In addition, the DC-SIGN ligand mannan and an anti-DC-SIGN antibody did not inhibit DC-mediated enhancement.
HIV-1 particles were internalized and were protected from protease treatment following binding to DCs, but not from binding
to DC-SIGN-expressing Raji cells. Thus, DC-SIGN is not required for DC-mediated trans-enhancement of HIV infectivity.

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Available from: César Boggiano, Feb 12, 2015
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    • "However, the carbohydrate structure on gp120 recognized by DCIR is unclear (Lambert et al., 2013). Furthermore, the importance of DC-SIGN in HIV-1 infection remains controversial (Boggiano et al., 2007; da Silva et al., 2011; Gummuluru et al., 2003). Given that DC-SIGN and DCIR both function in gp120 binding, we asked whether these two CLRs contribute equally or one over the other in DC-mediated HIV-1 capture and transfer. "
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    ABSTRACT: The C-type lectin receptors (CLRs) expressed on dendritic cells (DCs), in particular DC-SIGN and DCIR, likely play an important role in HIV-1 early infection. Here, we systematically compared the capture and transfer capability of DC-SIGN and DCIR using a wide range of HIV-1 isolates. Our results indicated that DC-SIGN plays a stronger role than DCIR in DC-mediated HIV-1 capture and transfer. This was further strengthened by the data from transient and stable transfectants, showing that DC-SIGN had better capability, compared with DCIR in HIV-1 capture and transfer. Following constructing and analyzing a series of soluble DC-SIGN and DCIR truncates and chimeras, we demonstrated that the neck domain, but not the CRD, renders DC-SIGN higher binding affinity to gp120 likely via the formation of tetramerization. Our findings provide insights into CLR-mediated HIV-1 capture and transfer, highlighting potential targets for intervention strategies against gp120-CLR interactions.
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    • "A later second phase is dependent on productive infection of DCs and storage of viral progeny. We have recently demonstrated that the C-type lectin receptor known as dendritic cell immunoreceptor or DCIR [16] allows HIV-1 to attach to DCs and enhances HIV-1 infection in both phases [17], unlike DC-SIGN (dendritic cell-specific intercellular adhesion molecule-3-grabbing non integrin), which is only involved in the early phase [18], [19]. Among the various HIV-1 cell surface receptors expressed in DCs, only DCIR has been shown to play a key role in viral dissemination, initiation of infection [17] and antiviral immunity [20]. "
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    PLoS ONE 07/2013; 8(7):e67873. DOI:10.1371/journal.pone.0067873 · 3.23 Impact Factor
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    • "HIV-1 Nef causes up-regulation of DC-SIGN in HIV-1-infected DCs (Sol-Foulon et al. 2002) and over-expression of HIV-1 Nef protein into HeLa cells causes up-regulation of surface DC-SIGN expression, by preventing DC-SIGN endocytosis (Sol- Foulon et al. 2002). Nef-upregulated DC-SIGN expression promotes HIV-1 transmission from HeLa cells to cocultured lymphocytes (Sol-Foulon et al. 2002), but DC-SIGN may play only a partial role in DC-mediated HIV-1 transmission to CD4 + T cells (Boggiano et al. 2007; Gurney et al. 2005; Wu et al. 2002). HIV-1 Nef expression in the context of virus infection promotes DC-mediated transmission of HIV-1 to CD4 + T cells, which correlates with decreased CD4 expression and only modest increases in DC-SIGN expression (St Gelais et al. 2012). "
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