Messmer D, Bromberg J, Devgan G, Jacqué J-M, Granelli-Piperno A, Pope M
North Shore LIJ Research Institute, Manhasset, New York 11030, USA.
AIDS Res Hum Retroviruses. 2002 Sep 20;18(14):1043-50. doi: 10.1089/08892220260235407.
Replication of immunodeficiency viruses (HIV-1 and SIV) in immature dendritic cell (DC)-T cell cocultures is dependent on Nef. In contrast, mature DCs promote the replication of wild-type and nef-defective SIV in concert with CD4(+) T cells. Transcription factor activation occurs on DC maturation and this study aimed to investigate whether Nef triggers similar events in immature DCs, rendering them more like mature DCs. Recombinant HIV nef-expressing adenovirus was used to selectively introduce nef into immature human or macaque DCs. These data provide the first evidence that the expression of HIV nef in immature DCs induced selective activation of STAT3 and, to a lesser extent, NF-kappaB. This highlights how Nef can signal primary immature DCs, suggesting one way in which Nef may modulate immature DCs to drive virus replication in the DC-T cell milieu.
免疫缺陷病毒(HIV-1和SIV)在未成熟树突状细胞(DC)与T细胞的共培养物中的复制依赖于Nef。相比之下,成熟DC与CD4(+) T细胞协同促进野生型和nef缺陷型SIV的复制。转录因子激活发生在DC成熟过程中,本研究旨在调查Nef是否会在未成熟DC中引发类似事件,使其更类似于成熟DC。使用表达重组HIV nef的腺病毒将nef选择性地导入未成熟的人或猕猴DC中。这些数据首次证明,HIV nef在未成熟DC中的表达诱导了STAT3的选择性激活,并在较小程度上诱导了NF-κB的激活。这突出了Nef如何向初级未成熟DC发出信号,提示了Nef可能调节未成熟DC以驱动DC-T细胞环境中病毒复制的一种方式。