African swine fever virus infects macrophages, the natural host cells, via clathrin- and cholesterol-dependent endocytosis

African swine fever virus infects macrophages, the natural host cells, via clathrin- and cholesterol-dependent endocytosis
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DOI:
10.1016/j.virusres.2015.01.022
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发表时间:
2015-03-16
期刊:
影响因子:
5
通讯作者:
Alonso, Covadonga
Alonso, Covadonga
中科院分区:
医学3区
文献类型:
--
作者:
Galindo, Inmaculada;Angel Cuesta-Geijo, Miguel;Alonso, Covadonga

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非洲猪瘟病毒(ASFV)的主要细胞靶点是猪巨噬细胞。然而,关于感染早期阶段的现有数据先前在非白细胞细胞如Vero细胞中表征。在这里,我们报告ASFV进入天然宿主细胞使用动力蛋白依赖性和网格蛋白介导的内吞作用。该途径在猪巨噬细胞感染的第一步期间具有强烈的pH依赖性。我们研究了药物抑制巨噬细胞内吞途径的作用,并将ASFV与痘苗病毒(VV)进行了比较,后者显然涉及不同的进入途径。细胞膜中胆固醇的存在被认为是必不可少的生产ASFV感染,而肌动蛋白依赖性的内吞作用和参与磷酸肌醇-3-激酶(PI 3 K)的活动是病毒进入的过程中所需的其他细胞因子。这些发现提高了我们对ASFV与巨噬细胞相互作用的理解,这些相互作用允许成功的病毒复制。(C)2015 Elsevier B. V.版权所有。
The main cellular target for African swine fever virus (ASFV) is the porcine macrophage. However, existing data about the early phases of infection were previously characterized in non-leukocyte cells such as Vero cells. Here, we report that ASFV enters the natural host cell using dynamin-dependent and clathrin-mediated endocytosis. This pathway is strongly pH-dependent during the first steps of infection in porcine macrophages. We investigated the effect of drugs inhibiting several endocytic pathways in macrophages and compared ASFV with vaccinia virus (VV), which apparently involves different entry pathways. The presence of cholesterol in cellular membranes was found to be essential for a productive ASFV infection while actin-dependent endocytosis and the participation of phosphoinositide-3-kinase (PI3K) activity were other cellular factors required in the process of viral entry. These findings improved our understanding of the ASFV interactions with macrophages that allow for successful viral replication. (C) 2015 Elsevier B.V. All rights reserved.