Center for Retrovirus Research, Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio, United States of America.
PLoS One. 2012;7(3):e34521. doi: 10.1371/journal.pone.0034521. Epub 2012 Mar 30.
HIV-1 Nef enhances dendritic cell (DC)-mediated viral transmission to CD4(+) T cells, but the underlying mechanism is not fully understood. It is also unknown whether HIV-1 infected DCs play a role in activating CD4(+) T cells and enhancing DC-mediated viral transmission. Here we investigated the role of HIV-1 Nef in DC-mediated viral transmission and HIV-1 infection of primary CD4(+) T cells using wild-type HIV-1 and Nef-mutated viruses. We show that HIV-1 Nef facilitated DC-mediated viral transmission to activated CD4(+) T cells. HIV-1 expressing wild-type Nef enhanced the activation and proliferation of primary resting CD4(+) T cells. However, when co-cultured with HIV-1-infected autologous DCs, there was no significant trend for infection- or Nef-dependent proliferation of resting CD4(+) T cells. Our results suggest an important role of Nef in DC-mediated transmission of HIV-1 to activated CD4(+) T cells and in the activation and proliferation of resting CD4(+) T cells, which likely contribute to viral pathogenesis.
HIV-1 Nef 增强树突状细胞（DC）介导的病毒向 CD4(+)T 细胞的传播，但其中的机制尚未完全阐明。此外，尚不清楚 HIV-1 感染的 DC 是否在激活 CD4(+)T 细胞和增强 DC 介导的病毒传播中发挥作用。在这里，我们使用野生型 HIV-1 和 Nef 突变病毒研究了 HIV-1 Nef 在 DC 介导的病毒传播和 HIV-1 感染原代 CD4(+)T 细胞中的作用。我们发现 HIV-1 Nef 促进了 DC 介导的病毒向激活的 CD4(+)T 细胞的传播。表达野生型 Nef 的 HIV-1 增强了原代静止 CD4(+)T 细胞的激活和增殖。然而，当与感染了 HIV-1 的自体 DC 共培养时，静止 CD4(+)T 细胞的感染或 Nef 依赖性增殖并没有明显的趋势。我们的研究结果表明，Nef 在 DC 介导的 HIV-1 向激活的 CD4(+)T 细胞的传播以及静止的 CD4(+)T 细胞的激活和增殖中发挥重要作用，这可能有助于病毒的发病机制。
