Ameobal pathogen mimivirus infects macrophages through phagocytosis.
Ameobal pathogen mimivirus infects macrophages through phagocytosis.
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DOI：
10.1371/journal.ppat.1000087
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发表时间：
2008-06-13
期刊：
影响因子：
6.7
通讯作者：
Raoult, Didier
中科院分区：
文献类型：
--
作者：
Ghigo, Eric;Kartenbeck, Juergen;Lien, Pham;Pelkmans, Lucas;Capo, Christian;Mege, Jean-Louis;Raoult, Didier
Mimi病毒，或称棘阿米巴多噬模拟病毒(APMV)，是一种生长在阿米巴中的巨大双链DNA病毒，于2003年首次被发现。阿米巴通过吞噬作用进入阿米巴，但尚未得到证实。我们在这里证明了APMV被巨噬细胞内化，而不是被非吞噬细胞内化，导致了APMV的有效复制。APMV不使用笼状蛋白和小窝蛋白介导的内吞途径以及降解的内小体介导的内吞作用来入侵巨噬细胞。超微结构分析显示，进入病毒的周围有突起形成，提示APMV的进入与巨噬细胞吞噬作用有关。APMV的进入需要肌动蛋白细胞骨架的重组和磷脂酰肌醇3-激酶的激活。阻断巨噬细胞吞噬和APMV缺乏与rabanyrin-5的共定位表明巨噬细胞吞噬不参与病毒的进入。过表达显性-阴性形式的动力蛋白-II，一种吞噬调节因子，抑制了APMV进入。综上所述，我们的数据表明APMV通过吞噬作用进入巨噬细胞，这是病毒进入细胞的一种新途径。这加强了阿米巴内病原体有可能感染巨噬细胞的范例。巨型(750 Nm)双链DNA病毒棘阿米巴多噬模拟病毒(APMV)可能是肺炎的原因。我们在这里证明了APMV被巨噬细胞内化，而不是被非吞噬细胞内化，导致了有效的复制。我们还发现APMV通过吞噬作用侵入巨噬细胞。这是病毒通过细菌和寄生虫通常使用的机制被巨噬细胞内化的第一个证据。这一发现为已知的病毒进入细胞的策略增加了一条补充途径。这表明阿米巴体内的病原体也会感染巨噬细胞。最后，我们可以假设APMV在肺泡巨噬细胞内复制，导致人和小鼠肺炎。
Mimivirus, or Acanthamoeba polyphaga mimivirus (APMV), a giant double-stranded DNA virus that grows in amoeba, was identified for the first time in 2003. Entry by phagocytosis within amoeba has been suggested but not demonstrated. We demonstrate here that APMV was internalized by macrophages but not by non-phagocytic cells, leading to productive APMV replication. Clathrin- and caveolin-mediated endocytosis pathways, as well as degradative endosome-mediated endocytosis, were not used by APMV to invade macrophages. Ultrastructural analysis showed that protrusions were formed around the entering virus, suggesting that macropinocytosis or phagocytosis was involved in APMV entry. Reorganization of the actin cytoskeleton and activation of phosphatidylinositol 3-kinases were required for APMV entry. Blocking macropinocytosis and the lack of APMV colocalization with rabankyrin-5 showed that macropinocytosis was not involved in viral entry. Overexpression of a dominant-negative form of dynamin-II, a regulator of phagocytosis, inhibited APMV entry. Altogether, our data demonstrated that APMV enters macrophages through phagocytosis, a new pathway for virus entry in cells. This reinforces the paradigm that intra-amoebal pathogens have the potential to infect macrophages. The giant (750 nm) double-stranded DNA virus Acanthamoeba polyphaga mimivirus (APMV) is likely responsible for pneumonia. We demonstrate here that APMV was internalized by macrophages but not by non-phagocytic cells, leading to productive replication. We also show that APMV invaded macrophages through phagocytosis. This is the first evidence that a virus is internalized by macrophages via a mechanism normally used by bacteria and parasites. This finding adds a supplementary pathway to already known strategies used by viruses to enter cells. This underlines that intra-amoebal pathogens also infect macrophages. Finally, we can hypothesize that APMV replicates within alveolar macrophages, leading to human and murine pneumonia.
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