Caveolin-1 mediated uptake via langerin restricts HIV-1 infection in human Langerhans cells

Retrovirology

Teunis B H Geijtenbeek³  Vincent Everts⁴  Wikky Tigchelaar¹  Donna Fluitsma²  Lot de Witte⁵  Esther M Zijlstra-Willems³  Carla M S Ribeiro³  Linda M van den Berg³ 

[1] Department of Cell Biology & Histology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands;Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands;Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, Amsterdam, 1105 AZ, The Netherlands;Department of Oral Cell Biology, Academic Center for Dentistry Amsterdam, University of Amsterdam and VU University Amsterdam, Amsterdam, The Netherlands;Department of Psychiatry, University Medical Center Utrecht, Utrecht, The Netherlands

关键词: Clathrin;    Caveolar uptake;    Birbeck granules;    Langerin;    Langerhans cells;    Caveolin-1;    HIV-1 restriction;   

Others  :  1132006
DOI  :  10.1186/s12977-014-0123-7

 received in 2014-04-13, accepted in 2014-12-04,  发布年份 2014

【 摘 要 】

Background

Human Langerhans cells (LCs) reside in foreskin and vaginal mucosa and are the first immune cells to interact with HIV-1 during sexual transmission. LCs capture HIV-1 through the C-type lectin receptor langerin, which routes the virus into Birbeck granules (BGs), thereby preventing HIV-1 infection. BGs are langerin-positive organelles exclusively present in LCs, however, their origin and function are unknown.

Results

Here, we not only show that langerin and caveolin-1 co-localize at the cell membrane and in vesicles but also that BGs are langerin/caveolin-1-positive vesicles are linked to the lysosomal degradation pathway in LCs. Moreover, inhibition of caveolar endocytosis in primary LCs abrogated HIV-1 sequestering into langerin⁺ caveolar structures. Notably, both inhibition of caveolar uptake and silencing of caveolar structure protein caveolin-1 resulted in increased HIV-1 integration and subsequent infection. In contrast, inhibition of clathrin-mediated endocytosis did not affect HIV-1 integration, even though HIV-1 uptake was decreased, suggesting that clathrin-mediated endocytosis is not involved in HIV-1 restriction in LCs.

Conclusions

Thus, our data strongly indicate that BGs belong to the caveolar endocytosis pathway and that caveolin-1 mediated HIV-1 uptake is an intrinsic restriction mechanism present in human LCs that prevents HIV-1 infection. Harnessing this particular internalization pathway has the potential to facilitate strategies to combat HIV-1 transmission.

【 授权许可】

   
2014 van den Berg et al.; licensee BioMed Central.

【 图 表 】

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