Department of Pathology, University of New Mexico School of Medicine, Albuquerque, NM, USA.
Virology. 2011 Apr 10;412(2):411-25. doi: 10.1016/j.virol.2011.01.024. Epub 2011 Feb 21.
Orthopoxviruses encode multiple proteins that modulate host immune responses. We determined whether cowpox virus (CPXV), a representative orthopoxvirus, modulated innate and acquired immune functions of human primary myeloid DCs and plasmacytoid DCs and monocyte-derived DCs (MDDCs). A CPXV infection of DCs at a multiplicity of infection of 10 was nonproductive, altered cellular morphology, and failed to reduce cell viability. A CPXV infection of DCs did not stimulate cytokine or chemokine secretion directly, but suppressed toll-like receptor (TLR) agonist-induced cytokine secretion and a DC-stimulated mixed leukocyte reaction (MLR). LPS-stimulated NF-κB nuclear translocation and host cytokine gene transcription were suppressed in CPXV-infected MDDCs. Early viral immunomodulatory genes were upregulated in MDDCs, consistent with early DC immunosuppression via synthesis of intracellular viral proteins. We conclude that a nonproductive CPXV infection suppressed DC immune function by synthesizing early intracellular viral proteins that suppressed DC signaling pathways.
正痘病毒编码多种调节宿主免疫反应的蛋白。我们确定牛痘病毒（CPXV）作为一种代表性的正痘病毒，是否能调节人原代髓样树突状细胞（myeloid dendritic cells，DCs）、浆细胞样 DCs 和单核细胞衍生的 DC（monocyte-derived DCs，MDDCs）的固有和获得性免疫功能。CPXV 对 DC 的感染倍数为 10 时是非增殖性的，改变细胞形态，并且不能降低细胞活力。CPXV 对 DC 的感染不能直接刺激细胞因子或趋化因子的分泌，但能抑制 Toll 样受体（toll-like receptor，TLR）激动剂诱导的细胞因子分泌和 DC 刺激的混合淋巴细胞反应（mixed leukocyte reaction，MLR）。在 CPXV 感染的 MDDCs 中，脂多糖（lipopolysaccharide，LPS）刺激的 NF-κB 核易位和宿主细胞因子基因转录被抑制。早期病毒免疫调节基因在 MDDCs 中上调，这与通过合成细胞内病毒蛋白导致早期 DC 免疫抑制一致。我们的结论是，非增殖性 CPXV 感染通过合成早期细胞内病毒蛋白来抑制 DC 的免疫功能，从而抑制 DC 信号通路。
