Center for Retrovirus Research, Department of Veterinary Bioscience, The Ohio State University, 1900 Coffey Road, Columbus, OH 43210, USA.
Retrovirology. 2011 Jul 8;8:55. doi: 10.1186/1742-4690-8-55.
Human myeloid-lineage cells are refractory to HIV-1 infection. The Vpx proteins from HIV-2 and sooty mangabey SIV render these cells permissive to HIV-1 infection through proteasomal degradation of a putative restriction factor. Two recent studies discovered the cellular protein SAMHD1 to be this restriction factor, demonstrating that Vpx induces proteasomal degradation of SAMHD1 and enhances HIV-1 infection in myeloid-lineage cells. SAMHD1 functions as a myeloid-cell-specific HIV-1 restriction factor by inhibiting viral DNA synthesis. Here we discuss the implications of these findings in delineating the mechanisms of HIV-1 restriction in myeloid-lineage cells and the potential role of Vpx in lentiviral pathogenesis.
人类髓系细胞对 HIV-1 感染具有抗性。HIV-2 的 Vpx 蛋白和黑长尾猴 SIV 使这些细胞能够通过蛋白酶体降解假定的限制因子而对 HIV-1 感染变得敏感。最近的两项研究发现细胞蛋白 SAMHD1 是这种限制因子，证明 Vpx 诱导 SAMHD1 的蛋白酶体降解并增强髓系细胞中的 HIV-1 感染。SAMHD1 通过抑制病毒 DNA 合成作为髓系细胞特异性 HIV-1 限制因子发挥作用。在这里，我们讨论了这些发现对阐明髓系细胞中 HIV-1 限制机制的意义以及 Vpx 在慢病毒发病机制中的潜在作用。
