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Updated: Jun 17, 2026
Humanized NOD/SCID/IL2rγnull (hu-NSG) Mouse Model for HIV Replication and Latency Studies
Published on: January 7, 2019
Mutz-3-derived Langerhans cells are a model to study HIV-1 transmission and potential inhibitors
Marein A W P de Jong1, Lot de Witte, Saskia J A M Santegoets
1Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Meibergdreef 9, Amsterdam, the Netherlands 1105AZ.
Insights
Mutz-3 derived Langerhans cells (Mu-LCs) effectively model human Langerhans cells. Carbohydrate blockers of DC-SIGN, not Langerin, show promise as HIV-1 microbicides by preventing transmission without impairing antiviral functions.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Sexual transmission is the primary route of Human Immunodeficiency Virus type 1 (HIV-1) infection.
- Dendritic cell (DC) subsets in the genital mucosa play critical roles in HIV-1 dissemination.
- Langerhans cells (LCs) capture and degrade HIV-1 via Langerin, while other DCs expressing DC-SIGN facilitate transmission.
Purpose of the Study:
- To investigate the utility of Mutz-3 derived LCs (Mu-LCs) as a model for studying HIV-1 transmission.
- To identify potential microbicides for preventing HIV-1 sexual transmission.
Main Methods:
- Phenotypic characterization of Mu-LCs compared to primary LCs.
- Assessment of HIV-1 transmission by Mu-LCs.
- Evaluation of the impact of Langerin and DC-SIGN inhibition on HIV-1 transmission and LC function.
Main Results:
- Mu-LCs phenotypically resemble primary human LCs.
- Mu-LCs exhibit inefficient HIV-1 transmission.
- Inhibiting Langerin enhanced HIV-1 transmission.
- Carbohydrate structures blocking DC-SIGN, but not Langerin, prevented HIV-1 transmission by DCs without affecting LC antiviral function.
Conclusions:
- Mu-LCs serve as a valuable and accessible model for investigating LC roles in HIV-1 transmission.
- DC-SIGN targeted carbohydrate structures are promising candidates for HIV-1 microbicides.
- These microbicides can prevent viral transmission without compromising the protective antiviral functions of LCs.
Abstract:
Sexual transmission is the primary route of HIV-1 infection, and DC subsets are thought to be involved in viral dissemination to T cells. In the genital mucosa, two main subsets of DCs are present: epithelial LCs capture and degrade HIV-1 through C-type lectin Langerin, whereas subepithelial DCs express DC-SIGN, which facilitates HIV-1 transmission to T cells. As there is currently no HIV-1 vaccine available, microbicides provide an alternative strategy to limit HIV-1 spread. However, research into the function of LCs is hampered by the low availability and donor differences. Here, we set out to investigate whether LCs derived from the Mutz-3 cell line (Mu-LCs) provide a valuable tool to investigate the role of LCs in HIV-1 transmission and identify suitable potential microbicides. We demonstrate that Mu-LCs phenotypically resemble human primary LCs; Mu-LCs do not transmit HIV-1 efficiently, and inhibition of Langerin enhances HIV-1 transmission to T cells. We show that carbohydrate structures blocking DC-SIGN but not Langerin are potential microbicides, as they prevent HIV-1 transmission by DCs but do not affect the antiviral function of LCs. Therefore, Mu-LCs are a suitable model to investigate the role of LCs in HIV-1 transmission and to screen potential microbicides.
