Department of Biological and Medical Sciences, Oxford Brookes University, Headington, Oxford, United Kingdom.
Oxford Expression Technologies Ltd, Oxford, United Kingdom.
PLoS Pathog. 2019 Jun 10;15(6):e1007827. doi: 10.1371/journal.ppat.1007827. eCollection 2019 Jun.
P10 is a small, abundant baculovirus protein that accumulates to high levels in the very late stages of the infection cycle. It is associated with a number of intracellular structures and implicated in diverse processes from occlusion body maturation to nuclear stability and lysis. However, studies have also shown that it is non-essential for virus replication, at least in cell culture. Here, we describe the use of serial block-face scanning electron microscopy to achieve high-resolution 3D characterisation of P10 structures within Trichoplusia ni TN-368 cells infected with Autographa californica multiple nucleopolyhedrovirus. This has enabled unparalleled visualisation of P10 and determined the independent formation of dynamic perinuclear and nuclear vermiform fibrous structures. Our 3D data confirm the sequence of ultrastructural changes that create a perinuclear cage from thin angular fibrils within the cytoplasm. Over the course of infection in cultured cells, the cage remodels to form a large polarised P10 mass and we suggest that these changes are critical for nuclear lysis to release occlusion bodies. In contrast, nuclear P10 forms a discrete vermiform structure that was observed in close spatial association with both electron dense spacers and occlusion bodies; supporting a previously suggested role for P10 and electron dense spacers in the maturation of occlusion bodies. We also demonstrate that P10 hyper-expression is critical for function. Decreasing levels of p10 expression, achieved by manipulation of promoter length, correlated with reduced P10 production, a lack of formation of P10 structures and a concomitant decrease in nuclear lysis.
P10 是一种小型、丰富的杆状病毒蛋白,在感染周期的晚期会大量积累。它与许多细胞内结构有关,并参与从包埋体成熟到核稳定性和裂解的多种过程。然而,研究还表明,它对病毒复制不是必需的,至少在细胞培养中是这样。在这里,我们描述了使用连续块面扫描电子显微镜对感染苜蓿银纹夜蛾多核多角体病毒的甘蓝夜蛾 TN-368 细胞中的 P10 结构进行高分辨率 3D 特征描述。这使得能够以前所未有的方式可视化 P10,并确定了动态核周和核蜿蜒纤维结构的独立形成。我们的 3D 数据证实了超微结构变化的顺序,这些变化在细胞质中从薄角纤维形成核周笼。在培养细胞中的感染过程中,笼状结构重塑为一个大的极化 P10 团块,我们认为这些变化对于核裂解以释放包埋体至关重要。相比之下,核内 P10 形成离散的蜿蜒结构,与电子致密间隔物和包埋体密切空间相关;支持 P10 和电子致密间隔物在包埋体成熟中的先前建议的作用。我们还证明了 P10 的高表达对于功能至关重要。通过操纵启动子长度来降低 p10 的表达水平,与 P10 产量的降低、P10 结构的形成减少以及核裂解的相应减少相关。