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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"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. "
[Show abstract][Hide abstract] 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.
Virology 06/2014; s 458–459(1):83–92. DOI:10.1016/j.virol.2014.04.016 · 3.32 Impact Factor
"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  allows HIV-1 to attach to DCs and enhances HIV-1 infection in both phases , unlike DC-SIGN (dendritic cell-specific intercellular adhesion molecule-3-grabbing non integrin), which is only involved in the early phase , . 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  and antiviral immunity . "
[Show abstract][Hide abstract] ABSTRACT: The HIV-1 pandemic continues to expand while no effective vaccine or cure is yet available. Existing therapies have managed to limit mortality and control viral proliferation, but are associated with side effects, do not cure the disease and are subject to development of resistance. Finding new therapeutic targets and drugs is therefore crucial. We have previously shown that the dendritic cell immunoreceptor (DCIR), a C-type lectin receptor expressed on dendritic cells (DCs), acts as an attachment factor for HIV-1 to DCs and contributes to HIV-1 transmission to CD4(+) T lymphocytes (CD4TL). Directly involved in HIV-1 infection, DCIR is expressed in apoptotic or infected CD4TL and promotes trans-infection to bystander cells. Here we report the 3D modelling of the extracellular domain of DCIR. Based on this structure, two surface accessible pockets containing the carbohydrate recognition domain and the EPS binding motif, respectively, were targeted for screening of chemicals that will disrupt normal interaction with HIV-1 particle. Preliminary screening using Raji-CD4-DCIR cells allowed identification of two inhibitors that decreased HIV-1 attachment and propagation. The impact of these inhibitors on infection of DCs and CD4TL was evaluated as well. The results of this study thus identify novel molecules capable of blocking HIV-1 transmission by DCs and CD4TL.
PLoS ONE 07/2013; 8(7):e67873. DOI:10.1371/journal.pone.0067873 · 3.23 Impact Factor
"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). "
[Show abstract][Hide abstract] ABSTRACT: Dendritic cells (DCs) play a key role in the initial infection and cell-to-cell transmission events that occur upon HIV-1 infection. DCs interact closely with CD4(+) T cells, the main target of HIV-1 replication. HIV-1 challenged DCs and target CD4(+) T cells form a virological synapse that allows highly efficient transmission of HIV-1 to the target CD4(+) T cells, in the absence of productive HIV-1 replication in the DCs. Immature and subsets of mature DCs show distinct patterns of HIV-1 replication and cell-to-cell transmission, depending upon the maturation stimulus that is used. The cellular and viral mechanisms that promote formation of the virological synapse have been the subject of intense study and the most recent progress is discussed here. Characterizing the cellular and viral factors that affect DC-mediated cell-to-cell transmission of HIV-1 to CD4(+) T cells is vitally important to understanding, and potentially blocking, the initial dissemination of HIV-1 in vivo.
Advances in Experimental Medicine and Biology 01/2013; 762:109-30. DOI:10.1007/978-1-4614-4433-6_4 · 1.96 Impact Factor