The Hippo signaling component LATS2 enhances innate immunity to inhibit HIV-1 infection through PQBP1-cGAS pathway
The Hippo signaling component LATS2 enhances innate immunity to inhibit HIV-1 infection through PQBP1-cGAS pathway
复制标题
Hippo信号成分LATS2通过PQBP1-cGAS途径增强先天免疫抑制HIV-1感染
DOI：
10.1038/s41418-021-00849-1
复制
发表时间：
2021-08-12
影响因子：
12.4
通讯作者：
Liu，Xinqi
中科院分区：
文献类型：
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作者：
He，Tian-Sheng;Dang，Longlong;Liu，Xinqi
作为动物生理学中最原始的信号通路，Hippo通路和先天免疫不仅在感知细胞状况或感染中起关键作用，而且在各种代谢物稳态和肿瘤发生中起关键作用。然而，细胞内稳态和抗病毒防御之间的相关性还没有得到很好的理解。核心激酶LATS 1/2在不同的细胞环境中可以增强或抑制抗肿瘤免疫。在本研究中，我们发现LATS 2可以与cGAS的辅因子PQBP 1相互作用，从而增强cGAS-STING介导的针对HIV-1攻击的天然免疫应答。LATS 2被观察到上调I型干扰素（IFN-I）和细胞因子响应HIV-1逆转录的DNA和抑制HIV-1感染。由于PQBP 1的参与，LATS 2在调节cGAS活性中的功能不像经典Hippo途径中那样依赖于下游的雅普/TAZ。验证了LATS 2的相关激酶活性，并确定了PQBP 1的潜在磷酸化位点。我们的研究建立了Hippo信号与先天免疫之间的新联系，从而可能为抗病毒治疗提供新的潜在干预靶点。
As the most primordial signaling pathway in animal physiology, the Hippo pathway and innate immunity play crucial roles not only in sensing cellular conditions or infections, but also in various metabolite homeostasis and tumorigenesis. However, the correlation between cellular homeostasis and antiviral defense is not well understood. The core kinase LATS1/2, could either enhance or inhibit the anti-tumor immunity in different cellular contexts. In this study, we found that LATS2 can interact with PQBP1, the co-factor of cGAS, thus enhanced the cGAS-STING mediated innate immune response to HIV-1 challenge. LATS2 was observed to upregulate type-I interferon (IFN-I) and cytokines in response to HIV-1 reverse-transcribed DNA and inhibited HIV-1 infection. Due to the involvement of PQBP1, the function of LATS2 in regulating cGAS activity is not relying on the downstream YAP/TAZ as that in the canonical Hippo pathway. The related kinase activity of LATS2 was verified, and the potential phosphorylation site of PQBP1 was identified. Our study established a novel connection between Hippo signaling and innate immunity, thus may provide new potential intervention target on antiviral therapeutics.