Yoshida Takeshi, Kao Sandra, Strebel Klaus
Viral Biochemistry Section, Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health Bethesda, MD, USA.
Front Microbiol. 2011 Feb 18;2:35. doi: 10.3389/fmicb.2011.00035. eCollection 2011.
The HIV-1 Vpu protein enhances the release of viral particles from the cell-surface in a cell-type specific manner. In the absence of Vpu, nascent virions remain tethered to the cell-surface in restricted cell-types. Recently, the human host factor BST-2/CD317/tetherin was found to be responsible for the inhibition of virus release. It was also reported that HIV-1 Vpu can target human BST-2 but is unable to interfere with the function of murine or simian BST-2. We performed a gain-of-function study to determine which of the differences between human and rhesus BST-2 account for the differential sensitivity to Vpu. We transferred human BST-2 sequences into rhesus BST-2 and assessed the resulting chimeras for inhibition of HIV-1 virus release and sensitivity to Vpu. We found that rhesus BST-2 carrying the transmembrane (TM) domain of human BST-2 is susceptible to HIV-1 Vpu. Finally, a single-amino-acid change in the rhesus BST-2 TM domain was sufficient to confer Vpu sensitivity.
HIV-1 Vpu蛋白以细胞类型特异性方式增强病毒颗粒从细胞表面的释放。在缺乏Vpu的情况下，新生病毒体在特定受限细胞类型中仍与细胞表面相连。最近发现，人类宿主因子BST-2/CD317/ tetherin负责抑制病毒释放。也有报道称，HIV-1 Vpu可靶向人类BST-2，但无法干扰小鼠或猴BST-2的功能。我们进行了一项功能获得性研究，以确定人类和恒河猴BST-2之间的哪些差异导致了对Vpu的不同敏感性。我们将人类BST-2序列转移到恒河猴BST-2中，并评估所得嵌合体对HIV-1病毒释放的抑制作用以及对Vpu的敏感性。我们发现携带人类BST-2跨膜（TM）结构域的恒河猴BST-2对HIV-1 Vpu敏感。最后，恒河猴BST-2 TM结构域中的单个氨基酸变化足以赋予其对Vpu的敏感性。
