HIV-1 Antagonism of CD317 Is Species Specific and Involves Vpu-Mediated Proteasomal Degradation of the Restriction Factor
HIV-1 Antagonism of CD317 Is Species Specific and Involves Vpu-Mediated Proteasomal Degradation of the Restriction Factor
复制标题
DOI：
10.1016/j.chom.2009.01.009
复制
发表时间：
2009-03-19
影响因子：
30.3
通讯作者：
Keppler, Oliver T.
中科院分区：
文献类型：
--
作者：
Goffinet, Christine;Allespach, Ina;Keppler, Oliver T.
哺乳动物编码抑制细胞水平病毒复制的蛋白质。反过来，某些病毒具有进化的基因，可以在功能上抵消这些内在限制。人CD317（BST-2/HM1.24/Tetherin）是一个限制因素，它阻止了从细胞表面释放1型人类免疫缺陷病毒型（HIV-1），并且可以通过HIV-1 VPU来克服。在这里，我们表明小鼠和大鼠CD317有效抑制HIV-1释放，但对VPU具有抗性。种间嵌合体发现，啮齿动物特异性的抗性和对VPU拮抗作用的人类特异性敏感性涉及CD317的所有三个主要结构域。为了促进病毒释放，VPU通过通过20S蛋白酶体加速其降解来消耗人CD317的细胞池，而不是啮齿动物直系同源物的细胞库。因此，HIV-1 VPU抑制了人类细胞中CD317抗病毒因子的表达，并且对该抑制的物种特异性抗性可能指导HIV感染的小动物模型的发展。
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. Inter-species 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.