Department of Immunology and Microbiology, Rush University Medical Center, Chicago, IL 60612, USA.
Cell Host Microbe. 2010 Nov 18;8(5):397-409. doi: 10.1016/j.chom.2010.10.008.
Natural killer (NK) cell degranulation in response to virus-infected cells is triggered by interactions between invariant NK cell surface receptors and their ligands on target cells. Although HIV-1 Vpr induces expression of ligands for NK cell activation receptor, NKG2D, on infected cells, this is not sufficient to promote lytic granule release. We show that triggering the NK cell coactivation receptor NK-T- and -B cell antigen (NTB-A) alongside NKG2D promotes NK cell degranulation. Normally, NK cell surface NTB-A binds to NTB-A on CD4+ T cells. However, HIV-1 Vpu downmodulates NTB-A on infected T cells. Vpu associates with NTB-A through its transmembrane region without promoting NTB-A degradation. Cells infected with HIV-1 Vpu mutant elicited at least 50% more NK cells to degranulate than wild-type virus. Moreover, NK cells have a higher capacity to lyse HIV-infected cells with a mutant Vpu. Thus, Vpu downmodulation of NTB-A protects the infected cell from lysis by NK cells.
自然杀伤 (NK) 细胞对病毒感染细胞的脱颗粒反应是由 NK 细胞表面受体的不变结构域与靶细胞上的配体相互作用触发的。尽管 HIV-1 Vpr 诱导感染细胞表达 NK 细胞激活受体 NKG2D 的配体，但这不足以促进溶酶体颗粒的释放。我们表明，与 NKG2D 一起触发 NK 细胞共激活受体 NK-T-和-B 细胞抗原 (NTB-A) 可促进 NK 细胞脱颗粒。正常情况下，NK 细胞表面的 NTB-A 与 CD4+T 细胞上的 NTB-A 结合。然而，HIV-1 Vpu 下调感染 T 细胞上的 NTB-A。Vpu 通过其跨膜区域与 NTB-A 结合，而不促进 NTB-A 的降解。感染 HIV-1 Vpu 突变体的细胞比野生型病毒引发至少 50%更多的 NK 细胞脱颗粒。此外，NK 细胞裂解携带突变 Vpu 的 HIV 感染细胞的能力更高。因此，Vpu 下调 NTB-A 可保护感染细胞免受 NK 细胞的裂解。
