Goffinet Christine, Allespach Ina, Homann Stefanie, Tervo Hanna-Mari, Habermann Anja, Rupp Daniel, Oberbremer Lena, Kern Christian, Tibroni Nadine, Welsch Sonja, Krijnse-Locker Jacomine, Banting George, Kräusslich Hans-Georg, Fackler Oliver T, Keppler Oliver T
Department of Virology, University of Heidelberg, Heidelberg, Germany.
Cell Host Microbe. 2009 Mar 19;5(3):285-97. doi: 10.1016/j.chom.2009.01.009.
Mammals encode proteins that inhibit viral replication at the cellular level. In turn, certain viruses have evolved genes that can functionally counteract these intrinsic restrictions. Human CD317 (BST-2/HM1.24/tetherin) is a restriction factor that blocks release of human immunodeficiency virus type 1 (HIV-1) from the cell surface and can be overcome by HIV-1 Vpu. Here, we show that mouse and rat CD317 potently inhibit HIV-1 release but are resistant to Vpu. Interspecies chimeras reveal that the rodent-specific resistance and human-specific sensitivity to Vpu antagonism involve all three major structural domains of CD317. To promote virus release, Vpu depletes cellular pools of human CD317, but not of the rodent orthologs, by accelerating its degradation via the 20S proteasome. Thus, HIV-1 Vpu suppresses the expression of the CD317 antiviral factor in human cells, and the species-specific resistance to this suppression may guide the development of small animal models of HIV infection.
哺乳动物编码在细胞水平抑制病毒复制的蛋白质。相应地，某些病毒已经进化出能够在功能上抵消这些内在限制的基因。人类CD317（BST-2/HM1.24/束缚素）是一种限制因子，可阻止1型人类免疫缺陷病毒（HIV-1）从细胞表面释放，并且HIV-1 Vpu可以克服这种限制。在此，我们表明小鼠和大鼠的CD317能有效抑制HIV-1释放，但对Vpu具有抗性。种间嵌合体表明，啮齿动物对Vpu拮抗作用的特异性抗性和人类的特异性敏感性涉及CD317的所有三个主要结构域。为促进病毒释放，Vpu通过经由20S蛋白酶体加速其降解来耗尽人类CD317的细胞池，但不会耗尽啮齿动物直系同源物的细胞池。因此，HIV-1 Vpu抑制人类细胞中CD317抗病毒因子的表达，并且对这种抑制的物种特异性抗性可能会指导HIV感染小动物模型的开发。
