IFI16 acts as a nuclear pathogen sensor to induce the inflammasome in response to Kaposi Sarcoma-associated herpesvirus infection.
IFI16 acts as a nuclear pathogen sensor to induce the inflammasome in response to Kaposi Sarcoma-associated herpesvirus infection.
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DOI：
10.1016/j.chom.2011.04.008
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发表时间：
2011-05-19
影响因子：
30.3
通讯作者：
Chandran B
中科院分区：
文献类型：
--
作者：
Kerur N;Veettil MV;Sharma-Walia N;Bottero V;Sadagopan S;Otageri P;Chandran B
炎症是包括病原体在内的外国分子的细胞质传感器，诱导caspase-1激活的功能和IL-1β细胞因子成熟。与Kaposi Sarma一起，我们证明了包括IL-1β在内的炎症微环境的血管增生肿瘤在内皮细胞的KSHV感染期间，干扰素γ诱导的蛋白16（IFI16）与适配器分子ASC和procaspase-1相互作用以形成功能性炎症体。 KSHV基因表达和/或潜在的KSHV基因组是炎症体激活所必需的，而IFI16与受感染的细胞核中的KSHV基因组共定位IFI16和ASC沉默减少了KSHV。
Inflammasomes are cytoplasmic sensors of foreign molecules, including pathogens, and function to induce caspase-1 activation and IL-1β cytokine maturation. Whether such a mechanism exists in the nucleus and is effective against nuclear replicating pathogens is unknown. Nuclear replicating herpesvirus KSHV is associated with Kaposi Sarcoma, an angioproliferative tumor characterized by an inflammatory microenvironment including IL-1β. We demonstrate that during KSHV infection of endothelial cells, interferon gamma-inducible protein 16 (IFI16) interacts with the adaptor molecule ASC and procaspase-1 to form a functional inflammasome. This complex was initially detected in the nucleus and subsequently in the peri-nuclear area. KSHV gene expression and/or latent KSHV genome is required for inflammasome activation and IFI16 colocalizes with the KSHV genome in the infected cell nucleus. Caspase-1 activation by KSHV was reduced by IFI16 and ASC silencing. Our studies reveal IFI16 as a nuclear pathogen sensor and demonstrate that the inflammasome also functions in the nucleus.
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DOI：
10.4049/jimmunol.0802367
发表时间：
2009-03-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Bryan NB;Dorfleutner A;Rojanasakul Y;Stehlik C
通讯作者：
Stehlik C
DOI：
10.1146/annurev-pathol-121808-102144
发表时间：
2010
期刊：
Annual review of pathology
影响因子：
--
作者：
Coppé JP;Desprez PY;Krtolica A;Campisi J
通讯作者：
Campisi J
影响因子：
16
作者：
Martinon, F;Burns, K;Tschopp, J
通讯作者：
Tschopp, J
影响因子：
30.5
作者：
Buerckstuemmer, Tilmann;Baumann, Christoph;Superti-Furga, Giulio
通讯作者：
Superti-Furga, Giulio
影响因子：
5.4
作者：
Sharma-Walia, N;Krishnan, HH;Chandran, B
通讯作者：
Chandran, B