Host-Pathogen Interactions, Paul-Ehrlich-Institute, 63225, Langen, Germany.
Immunity and Pathogenesis Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, 92037, USA.
Med Microbiol Immunol. 2019 Aug;208(3-4):513-529. doi: 10.1007/s00430-019-00593-x. Epub 2019 Mar 16.
SAMHD1 was initially described for its ability to efficiently restrict HIV-1 replication in myeloid cells and resting CD4 T cells. However, a growing body of evidence suggests that SAMHD1-mediated restriction is by far not limited to lentiviruses, but seems to be a general concept that applies to most retroviruses and at least a number of DNA viruses. SAMHD1 anti-viral activity was long believed to be solely due to its ability to deplete cellular dNTPs by enzymatic degradation. However, since its discovery, several new functions have been attributed to SAMHD1. It has been demonstrated to bind nucleic acids, to modulate innate immunity, as well as to participate in the DNA damage response and resolution of stalled replication forks. Consequently, it is likely that SAMHD1-mediated anti-viral activity is not or not exclusively mediated through its dNTPase activity. Therefore, in this review, we summarize current knowledge on SAMHD1 cellular functions and systematically discuss how these functions could contribute to the restriction of a broad range of viruses besides retroviruses: herpesviruses, poxviruses and hepatitis B virus. Furthermore, we aim to highlight different ways how viruses counteract SAMHD1-mediated restriction to bypass the SAMHD1-mediated block to viral infection.
SAMHD1 最初因其能够在髓系细胞和静止 CD4 T 细胞中有效限制 HIV-1 复制而被描述。然而，越来越多的证据表明，SAMHD1 介导的限制远不仅限于慢病毒，而是一种普遍的概念，适用于大多数逆转录病毒，至少适用于一些 DNA 病毒。SAMHD1 的抗病毒活性长期以来被认为仅仅是由于其通过酶降解消耗细胞 dNTP 的能力。然而，自发现以来，SAMHD1 已被证明具有结合核酸、调节先天免疫以及参与 DNA 损伤反应和停滞复制叉的解决等新功能。因此，SAMHD1 介导的抗病毒活性可能不是或不仅仅是通过其 dNTPase 活性介导的。因此，在这篇综述中，我们总结了 SAMHD1 的细胞功能的最新知识，并系统地讨论了这些功能如何有助于限制除逆转录病毒以外的广泛病毒：疱疹病毒、痘病毒和乙型肝炎病毒。此外，我们旨在强调病毒对抗 SAMHD1 介导的限制以绕过 SAMHD1 介导的病毒感染阻断的不同方式。
