National Engineering Laboratory for AIDS Vaccine, College of Life Science, Jilin University, Changchun, Jilin Province, People's Republic of China.
FEBS Lett. 2013 Jan 4;587(1):37-43. doi: 10.1016/j.febslet.2012.11.022. Epub 2012 Nov 28.
Tetherin/BST-2/CD317 inhibits HIV-1 release from infected cells, but the viral Vpu protein efficiently antagonizes this antiviral activity through direct interaction between the transmembrane (TM) domains of each protein. Here, we demonstrated that overexpression of an inactive tetherin delGPI mutant, the TM domain of which could competitively block Vpu targeting of endogenous tetherin, potently inhibited HIV-1 release from human tetherin-positive cells in both transient and stable expression conditions. These results also suggest that heterologous dimerization occurred between the delGPI mutant and endogenous tetherin. These findings suggest that blocking the Vpu/tetherin interface may be a novel therapeutic approach against HIV-1 release.
tetherin/BST-2/CD317 抑制感染细胞中 HIV-1 的释放，但病毒 Vpu 蛋白通过两种蛋白的跨膜 (TM) 域之间的直接相互作用，有效地拮抗这种抗病毒活性。在这里，我们证明了一种无活性 tetherin delGPI 突变体的过表达，其 TM 结构域可以竞争性地阻断 Vpu 对内源性 tetherin 的靶向，在瞬时和稳定表达条件下均能有效地抑制人 tetherin 阳性细胞中 HIV-1 的释放。这些结果还表明，delGPI 突变体和内源性 tetherin 之间发生了异源二聚化。这些发现表明，阻断 Vpu/tetherin 界面可能是一种针对 HIV-1 释放的新型治疗方法。
