Department of Microbiology and Immunology, Queen's University, Kingston, ON, Canada.
Vet Microbiol. 2010 Jan 6;140(1-2):9-17. doi: 10.1016/j.vetmic.2009.07.015. Epub 2009 Jul 10.
The macrophage (Mø) is an essential immune cell for innate immunity. Such cells are targeted by African swine fever virus (ASFV). The early phases of infection with ASFV have been previously characterized in non-leukocyte cells such as Vero cells. Here, we report on several additional key parameters that ASFV utilizes during the infection of primary Mø. Related to virus infection, we established that receptor-mediated endocytosis of the virus by Mø is not the exclusive means of entry to infect the host cells. Analysis of the ensuing processes identified divalent cation-dependent activities to be particularly important, relating to the virus requirement for microtubule assembly needed for endocytic and endosomal processing. Actin-dependent endocytosis and endocytic flux involving microtubule activity are also implicated, pointing to entry via phagocytosis. Subsequently, the virus avoids terminal degradation by circumventing mature lysosome activities, including autophagosome-lysosome delivery. Nevertheless, the replicative cycle is apparently dependent on certain lysosomal functions, i.e. activities sensitive to propylamine are essential for the virus, whereas vinblastine- and leupeptin-sensitive functions only partially influence viral replication. The present work has identified cellular processes essential for ASFV to infect and replicate in the macrophage. These findings will improve our understanding of the cellular pathways employed by viruses infecting immune scavenger cells.
巨噬细胞（Mø）是先天免疫的重要免疫细胞。这种细胞是非洲猪瘟病毒（ASFV）的靶标。ASFV 感染的早期阶段以前曾在非白细胞细胞（如 Vero 细胞）中得到描述。在这里，我们报告了 ASFV 在感染原代 Mø 期间利用的几个其他关键参数。与病毒感染有关，我们确定了 Mø 中病毒的受体介导的内吞作用不是感染宿主细胞的唯一进入方式。对随后发生的过程的分析确定二价阳离子依赖性活性特别重要，与病毒组装微管所需的内吞作用和内体处理有关。肌动蛋白依赖性内吞作用和涉及微管活性的内吞作用也被牵连，表明通过吞噬作用进入。随后，病毒通过绕过包括自噬体-溶酶体递送在内的成熟溶酶体活性来避免末端降解。尽管如此，复制周期显然依赖于某些溶酶体功能，即对丙胺敏感的活性对病毒至关重要，而长春花碱和亮肽素敏感的功能仅部分影响病毒复制。本研究鉴定了 ASFV 感染和在巨噬细胞中复制所必需的细胞过程。这些发现将提高我们对感染免疫吞噬细胞的病毒所利用的细胞途径的理解。
