SAMHD1是唯一已知的人体内dNTP水解酶，具有重要生物学功能。SAMHD1突变与自身免疫疾病AGS和多种肿瘤发生发展及耐药有密切关系。有报道称逆转座子LINE-1的异常活跃也与自身免疫疾病和肿瘤紧密相关。申请人在国际上首次报导了SAMHD1是LINE-1的全新调节蛋白，开展了这一国际前沿领域研究。更重要的是，与AGS和肿瘤相关的SAMHD1突变体失去了抑制LINE-1的功能，揭示LINE-1调节疾病的重要性。此外，SAMHD1另一个引人瞩目的功能是在巨噬细胞中的具有抗HIV活性，这一功能的发现与申请人30多年的科研经历尤其是HIV Vpx的发现与研究密切相关。本研究拟深入探讨SAMHD1抑制LINE-1以及SAMHD1抗HIV病毒活性的机制研究这一国际科研热点难点，揭示SAMHD1在抗HIV以及诱导自身免疫疾病和肿瘤中扮演的重要角色，为抗HIV治疗和抗肿瘤治疗提供新的理论依据。

SAMHD1, as the only dNTPase known in human, has critical biological functions. SAMHD1 mutations are involved in autoimmune diseases (AGS) and are closely associated with the genesis, development and drug resistance of tumor. Interestingly, retrotransposon LINE-1 activtion is also linked with autoimmune diseases and tumor. In the world, the applicant of this project firstly reported that SAMHD1 is the novel regulating protein of LINE-1. More importantly, SAMHD1 mutations, associated with AGS and tumor, cannot inhibit LINE-1 function, revealing the importance of LINE-1 regulation by SAMHD1. This study will delve into the new mechanisms of SAMHD1 mediated LINE-1 inhibition. Another striking function of SAMHD1 is that SAMHD1 can prohibit HIV replication in macrophage. This new function closely relates to the 30-year research experience of the applicant especialy the discovery of Vpx and its functional study leading to the discovery of SAMHD1 as a unique inhibitor of HIV in macrophages. This research will continue to study new mechanisms of SAMHD1 mediated HIV suppression which is a leading and popular research field.