Dendritic cell immunoreceptor is a new target for anti-AIDS drug development: identification of DCIR/HIV-1 inhibitors.
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 ther...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3706466?pdf=render |
| _version_ | 1818525968283729920 |
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| author | Alexandra A Lambert Arezki Azzi Sheng-Xiang Lin Geneviève Allaire Karianne P St-Gelais Michel J Tremblay Caroline Gilbert |
| author_facet | Alexandra A Lambert Arezki Azzi Sheng-Xiang Lin Geneviève Allaire Karianne P St-Gelais Michel J Tremblay Caroline Gilbert |
| author_sort | Alexandra A Lambert |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-11T06:16:26Z |
| format | Article |
| id | doaj.art-5a74cf007ed9420d92aaefcff076fb46 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T06:16:26Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-5a74cf007ed9420d92aaefcff076fb462022-12-22T01:17:58ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0187e6787310.1371/journal.pone.0067873Dendritic cell immunoreceptor is a new target for anti-AIDS drug development: identification of DCIR/HIV-1 inhibitors.Alexandra A LambertArezki AzziSheng-Xiang LinGeneviève AllaireKarianne P St-GelaisMichel J TremblayCaroline GilbertThe 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.http://europepmc.org/articles/PMC3706466?pdf=render |
| spellingShingle | Alexandra A Lambert Arezki Azzi Sheng-Xiang Lin Geneviève Allaire Karianne P St-Gelais Michel J Tremblay Caroline Gilbert Dendritic cell immunoreceptor is a new target for anti-AIDS drug development: identification of DCIR/HIV-1 inhibitors. PLoS ONE |
| title | Dendritic cell immunoreceptor is a new target for anti-AIDS drug development: identification of DCIR/HIV-1 inhibitors. |
| title_full | Dendritic cell immunoreceptor is a new target for anti-AIDS drug development: identification of DCIR/HIV-1 inhibitors. |
| title_fullStr | Dendritic cell immunoreceptor is a new target for anti-AIDS drug development: identification of DCIR/HIV-1 inhibitors. |
| title_full_unstemmed | Dendritic cell immunoreceptor is a new target for anti-AIDS drug development: identification of DCIR/HIV-1 inhibitors. |
| title_short | Dendritic cell immunoreceptor is a new target for anti-AIDS drug development: identification of DCIR/HIV-1 inhibitors. |
| title_sort | dendritic cell immunoreceptor is a new target for anti aids drug development identification of dcir hiv 1 inhibitors |
| url | http://europepmc.org/articles/PMC3706466?pdf=render |
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