研究人员发现一种叫做环-GMP-AMP合成酶(简称cGAS)的特殊的酶可作为一种应对HIV及其它逆转录病毒的免疫感测器,它会在出现第一个感染迹象时拉响警报。尽管人们在逆转录病毒中有着巨大的生物医学兴趣,但人们就身体对就逆转录病毒的先天免疫反应仍然知之甚少,而它又转而阻碍了疫苗的研发。到目前为止,存在于宿主中的、能够探测到包括HIV在内的逆转录病毒的感测器大体上是未知的。但Daxing Gao及其同事用原代人类细胞显示,HIV的逆转录——这是一个病毒复制所需的过程——会引起cGAS触发一种针对它的先天免疫反应,该反应涉及干扰素的产生。他们说,缺乏该酶的细胞无法检测到HIV、SIV及小鼠白血病病毒(MLV)。他们的发现意味着cGAS可作为HIV以及许多其它逆转录病毒的一种免疫感测器,而研究人员提出,应该对cGAS的产物——环-GMP-AMP——进行是否具有任何治疗功效的研究。他们所提供的对身体感测HIV的先天免疫的了解可能在未来有助于疫苗的研发。(生物谷 Bioon.com)
生物谷推荐的英文摘要
Science DOI: 10.1126/science.1240933
Cyclic GMP-AMP Synthase Is an Innate Immune Sensor of HIV and Other Retroviruses
Daxing Gao1, Jiaxi Wu1, You-Tong Wu1, Fenghe Du1,2, Chukwuemika Aroh3,4, Nan Yan3,4, Lijun Sun1,2, Zhijian J. Chen
Retroviruses, including HIV, can activate innate immune responses, but the host sensors for retroviruses are largely unknown. Here, we show that HIV infection activates cyclic-GMP–AMP (cGAMP) synthase (cGAS) to produce cGAMP, which binds to and activates the adaptor protein STING to induce type-I interferons and other cytokines. Inhibitors of HIV reverse transcriptase, but not integrase, abrogated interferon-β induction by the virus, suggesting that the reverse transcribed HIV DNA triggers the innate immune response. Knockout or knockdown of cGAS in mouse or human cell lines blocked cytokine induction by HIV, murine leukemia virus (MLV), and simian immunodeficiency virus (SIV). These results indicate that cGAS is an innate immune sensor of HIV and other retroviruses.