Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China.
Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, China.
mBio. 2024 Oct 16;15(10):e0167524. doi: 10.1128/mbio.01675-24. Epub 2024 Sep 6.
SAMHD1 is an intrinsic limiting factor that effectively prevents HIV-1 infection in macrophages, dendritic cells, and resting CD4+ T cells. Extensive studies have underscored the indispensable role of the dNTPase activity of SAMHD1 in its antiviral function by primarily depleting dNTPs in quiescent cells, thereby impeding HIV-1 cDNA synthesis. However, recent advancements in understanding posttranslational modifications of SAMHD1 have revealed specific modification site mutants that maintain their ability to reduce dNTP levels while impairing the inhibition of HIV-1 replication. Thus, the precise anti-HIV-1 mechanism of SAMHD1 remains enigmatic, necessitating a comprehensive understanding of the underlying mechanisms to develop novel therapeutic strategies targeting its antiviral activity. Recent findings by Guo et al. shed light on the role of SAMHD1 as an HIV-1 core sensor in suppressing HIV-1 infection after viral cDNA synthesis through its interaction with MX2 (H. Guo, W. Yang, H. Li, J. Yang, et al., mBio 15:e01363-24, 2024, https://doi.org/10.1128/mbio.01363-24).
SAMHD1 是一种内在的限制因素，可有效防止 HIV-1 感染巨噬细胞、树突状细胞和静止的 CD4+T 细胞。大量研究强调了 SAMHD1 的 dNTP 酶活性在其抗病毒功能中的不可或缺作用，主要通过耗尽静止细胞中的 dNTP 来阻碍 HIV-1 cDNA 的合成。然而，最近对 SAMHD1 的翻译后修饰的研究进展揭示了特定的修饰位点突变体，它们能够保持降低 dNTP 水平的能力，同时损害 HIV-1 复制的抑制作用。因此，SAMHD1 的精确抗 HIV-1 机制仍然是一个谜，需要全面了解其潜在机制，以开发针对其抗病毒活性的新型治疗策略。最近 Guo 等人的发现揭示了 SAMHD1 作为 HIV-1 核心传感器的作用，通过与 MX2 的相互作用，在病毒 cDNA 合成后抑制 HIV-1 感染（H. Guo, W. Yang, H. Li, J. Yang, 等人，mBio 15:e01363-24, 2024, https://doi.org/10.1128/mBio.01363-24）。
