Baculovirus actin-rearrangement-inducing factor ARIF-1 induces the formation of dynamic invadosome clusters.
Baculovirus actin-rearrangement-inducing factor ARIF-1 induces the formation of dynamic invadosome clusters.
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DOI：
10.1091/mbc.e20-11-0705
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发表时间：
2021-08-01
影响因子：
3.3
通讯作者：
Welch MD
中科院分区：
文献类型：
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作者：
Lauko DI;Ohkawa T;Mares SE;Welch MD
鳞翅目昆虫的病原-多核多角体病毒(AcMNPV)对寄主细胞的肌动蛋白骨架有明显的依赖性。在感染的延迟-早期阶段，AcMNPV被证明能诱导感染细胞的皮层肌动蛋白的积累。然而，皮质肌动蛋白组装的动力学和分子机制尚不清楚。在这里，我们证明了AcMNPV诱导了动态的点状肌动蛋白结构的皮质簇，这些结构介导了底层细胞外基质的降解，因此功能类似于哺乳动物细胞中的入侵体簇。此外，我们发现AcMNPV蛋白肌动蛋白重排诱导因子-1(ARIF-1)是昆虫宿主体内皮质肌动蛋白组装和有效病毒感染的必要条件和充分条件，对于侵染体的形成既是必要的也是充分的。我们绘制了ARIF-1的C-末端细胞质区域内的入侵小体形成所需的序列，并确定了组织这些结构所需的单个酪氨酸和脯氨酸残基。此外，我们还发现ARIF-1和与侵袭体相关的蛋白质Cortactin和Arp2/3复合体定位于侵袭体，而Arp2/3复合体的形成是必需的。这些ARIF-1诱导的侵染体可能对ARIF-1在全身性病毒传播中的作用起重要作用。
The baculovirus Autographa californica multiple nucleopolyhedrovirus (AcMNPV), a pathogen of lepidopteran insects, has a striking dependence on the host cell actin cytoskeleton. During the delayed-early stage of infection, AcMNPV was shown to induce the accumulation of actin at the cortex of infected cells. However, the dynamics and molecular mechanism of cortical actin assembly remained unknown. Here, we show that AcMNPV induces dynamic cortical clusters of dot-like actin structures that mediate degradation of the underlying extracellular matrix and therefore function similarly to clusters of invadosomes in mammalian cells. Furthermore, we find that the AcMNPV protein actin-rearrangement-inducing factor-1 (ARIF-1), which was previously shown to be necessary and sufficient for cortical actin assembly and efficient viral infection in insect hosts, is both necessary and sufficient for invadosome formation. We mapped the sequences within the C-terminal cytoplasmic region of ARIF-1 that are required for invadosome formation and identified individual tyrosine and proline residues that are required for organizing these structures. Additionally, we found that ARIF-1 and the invadosome-associated proteins cortactin and the Arp2/3 complex localize to invadosomes and Arp2/3 complex is required for their formation. These ARIF-1–induced invadosomes may be important for the function of ARIF-1 in systemic virus spread.