登革熱是一種由蚊子媒介傳染的急性發作但可自然痊癒的病毒性傳染病，登革病毒感染有可能是類似感冒發燒造成較輕微的登革熱或具威脅性會致命的登革出血熱/登革休克症狀，目前並無有效抗病毒治療法及疫苗。最近登革病毒目標細胞的研究顯示，單核球/巨噬細胞、神經細胞、肝臟細胞、內皮細胞、血球細胞株、週邊血液B淋巴細胞以及樹狀突細胞，都可能是登革病毒感染的目標，至於受感染的目標細胞在登革病毒致病機轉中所扮演角色及其影響仍究不明。由於樹狀突細胞在病毒感染產生免疫反應的機制中扮演重要的調控角色，故其活體內是否可被登革病毒感染是相當重要的課題。我們以顆粒球/巨噬細胞聚落刺激因子培養源自骨髓小鼠樹狀突細胞，再以登革二型病毒感染之，發現感染後24小時只在以OptiPrepTM梯度純化的低密度樹狀突細胞族群中測得代表病毒正在複製的負股核酸及病毒抗原。顯示只有極少數細胞被感染且容許登革二型病毒複製，我們同時測得樹狀突細胞產生大量α干擾素可能導致病毒不易在其內複製。為模擬蚊子叮咬皮膚自然感染的情形，我們將登革二型病毒直接皮下給予腳掌，觀察皮膚組織特化樹狀突細胞可否被登革病毒感染或擷取病毒抗原而移行至淋巴結藉此感染其他細胞。發現淋巴結懸浮液以OptiPrepTM梯度純化分離，低密度細胞族群中CD11c+Gr-1-細胞約佔40~50%為樹狀突細胞，13、17小時各測得約0.01%的細胞表現登革核心蛋白，除為CD205+樹狀突細胞外，也觀察數顆病毒蛋白陽性反應並不表現CD205的細胞。為增加小鼠被登革病毒感染我們於腳掌給予能生產病毒的小鼠肝癌細胞株，12、18小時於腿部淋巴結切片也偵測到登革病毒核心蛋白、外套膜蛋白表現細胞，進一步雙染細胞協同刺激分子CD86，初步認為表現病毒蛋白的細胞為抗原呈獻細胞一員。

Dengue virus (DV), an arthropod-borne flavivirus, causes a febrile illness or severe hemorrhagic fever for which there is no effective antiviral treatment and no vaccine available. It is still not clearly understood which tissue cells are the natural targets of DV. In addition to monocytes/ macrophages, neuron, hepatocytes, endothelial cells, B lymphcytes and dendritic cells have also been reported as potential targets for DV. Recent studies have demonstrated two subsets of dendritic cells, monocyte-derived dendritic cells and human skin Langerhans cells are targets for dengue virus infection. We are interested whether mouse dendritic cells can be infected by DV. Large numbers of dendritic cells from mouse bone marrow cultures supplemented with Granulocyte/ Macrophage Colony-stimulating Factor (GM-CSF) were generated. We found that bone marrow-derived dendritic cells (BMDC) can be infected with dengue virus. At 24 hours post-infection, negative- and positive-strand viral genome was detected on low density BMDC by RT-PCR, viral antigens were also detected by immunofluorescence analysis. The efficiency of DV infection on BMDC was extremely low, because BMDC express Type 1 Interferon. Furthermore, DV was injected subcutaneously into mouse skin to mimic mosquito bite. The spread of DV from inoculation site to the draining lymph node was characterized. The lymph node dendritic cells were isolated by optiprep gradient and the viral antigen was analyzed by immunofluorescence assays. The efficiency of DV infection on mouse cells was extremely low. A mouse hepatoma cell ML-15a can support dengue virus replication. This DV2 infected-ML-15a cell was inoculated into mouse footpad. DV viral antigens positive cell that express CD86 can be detected in draining lymph node.

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