Mo Mei, Chen Jiannan, Yang Yushan, Yu Yinyin, Wu Wenbi, Yang Kai, Yuan Meijin
State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
J Virol. 2024 Nov 19;98(11):e0113524. doi: 10.1128/jvi.01135-24. Epub 2024 Oct 21.
Autographa californica multiple nucleopolyhedrovirus (AcMNPV) () is highly conserved in baculoviruses. Previous studies have shown that is required for the production of infectious budded virions (BVs). However, the functional role of in virion morphogenesis remains unknown. In this report, an knockout virus and an repair virus were constructed. The effect of deletion on virion morphogenesis was investigated, and the expression and subcellular localization of the Ac106 protein were characterized. Our data indicated that is required for the nuclear egress of nucleocapsids and intranuclear microvesicle formation, as well as subsequent BV and occlusion-derived virion (ODV) production and the embedding of ODVs into polyhedra. Ac106 is a baculovirus late protein that is concentrated in discrete foci of virus-induced membrane structures in the intranuclear ring zone of virus-infected cells. Further studies on the relationship between Ac106 and four other proteins that are also required for intranuclear microvesicle formation, Ac75, Ac76, Ac93, and P48 (Ac103), revealed that Ac106 is associated with Ac75, Ac76, Ac93, P48, and itself. Ac106 is required for Ac75, Ac93, and P48 accumulation in foci of virus-induced intranuclear membrane structures and the intranuclear transport of Ac76. Analysis of the subcellular localization of ODV integral envelope proteins upon deletion of the genes required for intranuclear microvesicle formation indicated that intranuclear microvesicle formation may be essential for ODV integral envelope protein transport into the nucleus, supporting the hypothesis that intranuclear microvesicles originate from the nuclear membrane.IMPORTANCEBaculovirus occlusion-derived virions (ODVs) are known to acquire their envelopes from virus-induced intranuclear microvesicles within the nucleoplasm, and this strategy of intranuclear envelopment of nucleocapsids to form virions is unique among viruses. However, the mechanism of ODV morphogenesis, particularly intranuclear microvesicle formation, remains unclear. In this study, we identified as the fifth gene, in addition to , , , and (), which are required for intranuclear microvesicle formation. Further studies on the relationship between and the other four genes, as well as the effect of or deletion on the localization of ODV integral envelope proteins, indicated that intranuclear microvesicle formation may be essential for the transport of ODV integral envelope proteins into the nucleus, which strongly supports the hypothesis that intranuclear microvesicles originate from the nuclear membrane. These findings greatly enhance our understanding of the molecular mechanism of baculovirus ODV morphogenesis.
苜蓿银纹夜蛾多核多角体病毒（AcMNPV）在杆状病毒中高度保守。先前的研究表明，其对于感染性出芽病毒粒子（BVs）的产生是必需的。然而，其在病毒粒子形态发生中的功能作用仍不清楚。在本报告中，构建了一个Ac106基因敲除病毒和一个Ac106修复病毒。研究了Ac106缺失对病毒粒子形态发生的影响，并对Ac106蛋白的表达和亚细胞定位进行了表征。我们的数据表明，Ac106对于核衣壳的核输出和核内微泡形成是必需的，以及随后的BV和包涵体衍生病毒粒子（ODV）的产生以及ODV嵌入多角体也是必需的。Ac106是一种杆状病毒晚期蛋白，集中在病毒感染细胞内核环区病毒诱导的膜结构的离散焦点中。对Ac106与核内微泡形成也必需的其他四种蛋白Ac75、Ac76、Ac93和P48（Ac103）之间关系的进一步研究表明，Ac106与Ac75、Ac76、Ac93、P48以及其自身相关联。Ac106是Ac75、Ac并支持核内微泡起源于核膜的假说。
重要性
已知杆状病毒包涵体衍生病毒粒子（ODV）从核质内病毒诱导的核内微泡获得其包膜，并且这种核衣壳在核内包被形成病毒粒子的策略在病毒中是独特的。然而，ODV形态发生的机制，特别是核内微泡形成，仍不清楚。在本研究中，我们鉴定出Ac106是除Ac75、Ac76、Ac93和P48（Ac103）之外核内微泡形成所需的第五个基因。对Ac106与其他四个基因之间关系以及Ac106或Ac103缺失对ODV整合包膜蛋白定位的影响的进一步研究表明，核内微泡形成对于ODV整合包膜蛋白转运到细胞核可能是必不可少的，这有力地支持了核内微泡起源于核膜的假说。这些发现极大地增进了我们对杆状病毒ODV形态发生分子机制的理解。 93和P48在病毒诱导的核内膜结构焦点中的积累以及Ac76的核内运输是必需的。对核内微泡形成所需基因缺失时ODV整合包膜蛋白亚细胞定位的分析表明，核内微泡形成对于ODV整合包膜蛋白转运到细胞核可能是必不可少的，这
