Ayyavoo V, Mahboubi A, Mahalingam S, Ramalingam R, Kudchodkar S, Williams W V, Green D R, Weiner D B
Department of Pathology, University of Pennsylvania, Philadelphia 19104, USA.
Nat Med. 1997 Oct;3(10):1117-23. doi: 10.1038/nm1097-1117.
The HIV-1 accessory gene product Vpr can influence viral pathogenesis by affecting viral replication as well as host cell transcription and proliferation. We have investigated the effects of Vpr on host cell activation and confirm that it influences cellular proliferation. However, we have also found that Vpr modulates T-cell receptor (TCR)-triggered apoptosis in a manner similar to that of glucocorticoids. In the absence of TCR-mediated activation, Vpr induces apoptosis whereas in its presence, Vpr interrupts the expected induction of apoptosis. This regulation of apoptosis is linked to Vpr suppression of NF-kappa B activity via the induction of I kappa B, an inhibitor of NF-kappa B. Further, Vpr suppresses expression of IL-2, IL-10, IL-12, TNF alpha and IL-4, all of which are NF-kappa B-dependent. The effects of Vpr could be reversed by RU486. Our finding that Vpr can regulate NF-kappa B supports the hypothesis that some aspects of viral pathogenesis are the consequence of cell dysregulation by Vpr.
HIV-1辅助基因产物Vpr可通过影响病毒复制以及宿主细胞转录和增殖来影响病毒发病机制。我们研究了Vpr对宿主细胞活化的影响，并证实它会影响细胞增殖。然而，我们还发现Vpr以类似于糖皮质激素的方式调节T细胞受体（TCR）触发的细胞凋亡。在没有TCR介导的活化的情况下，Vpr诱导细胞凋亡，而在其存在的情况下，Vpr会中断预期的细胞凋亡诱导。这种细胞凋亡的调节与Vpr通过诱导IκB（一种NF-κB抑制剂）抑制NF-κB活性有关。此外，Vpr抑制IL-2、IL-10、IL-12、TNFα和IL-4的表达，所有这些都依赖于NF-κB。Vpr的作用可以被RU486逆转。我们发现Vpr可以调节NF-κB，这支持了病毒发病机制的某些方面是Vpr导致细胞失调的结果这一假设。
