A cryptic sensor for HIV-1 activates antiviral innate immunity in dendritic cells (Nature, 2010, 467:214-217)

報告日期: 2011/03/15
報告時間: 17:10/18:00
報告學生: 李原聰
講評老師: 葉才明

Full text: http://basicmed.med.ncku.edu.tw/admin/up_img/000315-3.pdf

A cryptic sensor for HIV-1 activates antiviral innate immunity in dendritic cells
Nicolas Manel , Brandon Hogstad, Yaming Wang , David E. Levy , Derya Unutmaz & Dan R. Littman
Nature. 2010 Sep 9; 467(7312):214-7.

Time: 17:10-18:00
Place: 602

Dendritic cells are considered to connect innate immunity and adaptive immune responses to defend our body from pathogen. However, human immunodeficiency virus-1(HIV-1), a well-known notorious retrovirus, can avoid the detection of dendritic cells and target CD4+ T-cells by “not to” replicate in dendritic cells. The authors intended to figure out whether dendritic cells could function normally after infected efficiently by HIV-1, to detect the virus and trigger adaptive immunity. The results show that with the help of SIV-VLP(G), dendritic cells can be transduced effectively by HIV-1. Moreover, dendritic cells were activated after the co-infection. The authors then used genome wide expression profiling to demonstrate which response was induced after infected by SIV-VLP and HIV-1. The results shows that a type I interferon (IFN) response was induced after the co-infection. They also found that newly synthesized GagPol protein is required for dendritic cell activation through type I IFN pathway, newly synthesized Gagpol interacts with CYPA, a peptidylprolyl isomerase required for optimal HIV-1 infectivity, activates phosphorylation of IRF3. After phosphorylated, IRF3 translocate to nucleus and promote the transcription of IFN-β and activates dendritic cells. Finally, the authors checked the contribution of co-stimulation to T-cell activation by co-culture with co-infected dendritic cells. The results show that co-infected dendritic cells can stimulate T-cell proliferation which is dependent on newly synthesized GagPol. To sum up, the authors discovered an “inner eye” of dendritic cells to detect HIV-1 infection and activate adaptive immunity. The mechanism described in this article may provide us a new direction to design the vaccine against HIV-1.

1. Steinman, R. M. & Hemmi, H. Dendritic cells: translating innate to adaptive immunity. Curr. Top. Microbiol. Immunol. 311, 17–58 (2006).
2. Takeuchi, O. & Akira, S. Innate immunity to virus infection. Immunol. Rev. 227, 75–86 (2009)