Unraveling the Entry Mechanism of Baculoviruses and Its Evolutionary Implications
Unraveling the Entry Mechanism of Baculoviruses and Its Evolutionary Implications
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DOI：
10.1128/jvi.03204-13
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发表时间：
2013-12
影响因子：
5.4
通讯作者：
Manli Wang;Jue Wang;F. Yin;Ying Tan;F. Dèng;Xinwen Chen;J. Jehle;J. Vlak;Zhìhóng Hú;Huálín Wáng
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文献类型：
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作者：
Manli Wang;Jue Wang;F. Yin;Ying Tan;F. Dèng;Xinwen Chen;J. Jehle;J. Vlak;Zhìhóng Hú;Huálín Wáng
摘要杆状病毒芽生病毒进入宿主细胞是由两种不同类型的包膜融合蛋白(EFP)介导的，即GP64和F蛋白。系统进化分析表明，F蛋白是祖先杆状病毒EFP，而GP64是较新获得的I群甲型杆状病毒，可能刺激了I群谱系的形成。这项研究旨在实验性地概括杆状病毒进化中可能的一个主要步骤。我们证明了F基因缺失的第二组甲型杆状病毒(棉铃虫核型多角体病毒[HearNPV])的感染性可以通过将GP64与来自心脏NPV的非融合基因Fdef(Furin位点突变的HAF)共插入而在功能上被挽救。有趣的是，心脏核型多角体病毒通过内吞作用进入细胞，在低pH值下通过直接膜融合进入细胞，效率较低。然而，这种共表达Fdef和GP64的重组HearNPV不仅在EFP组成上模拟了I组病毒，而且在低pH触发的直接融合途径中也模仿了它进入宿主细胞的能力。中和实验表明，非融合性F蛋白主要参与与敏感细胞的结合，而GP64则主要参与融合。将GP64与来自第I组病毒的类F蛋白(Ac23)共插入，可有效地挽救第II组F-空病毒。综上所述，这些重组病毒及其进入方式被认为类似于祖先I组病毒获得GP64并随后适应性失活原始F蛋白的进化事件。这里描述的研究提供了第一个支持杆状病毒EFP进化假说的实验证据。
ABSTRACT The entry of baculovirus budded virus into host cells is mediated by two distinct types of envelope fusion proteins (EFPs), GP64 and F protein. Phylogenetic analysis suggested that F proteins were ancestral baculovirus EFPs, whereas GP64 was acquired by progenitor group I alphabaculovirus more recently and may have stimulated the formation of the group I lineage. This study was designed to experimentally recapitulate a possible major step in the evolution of baculoviruses. We demonstrated that the infectivity of an F-null group II alphabaculovirus (Helicoverpa armigera nucleopolyhedrovirus [HearNPV]) can be functionally rescued by coinsertion of GP64 along with the nonfusogenic Fdef (furin site mutated HaF) from HearNPV. Interestingly, HearNPV enters cells by endocytosis and, less efficiently, by direct membrane fusion at low pH. However, this recombinant HearNPV coexpressing Fdef and GP64 mimicked group I virus not only in its EFP composition but also in its abilities to enter host cells via low-pH-triggered direct fusion pathway. Neutralization assays indicated that the nonfusogenic F proteins contribute mainly to binding to susceptible cells, while GP64 contributes to fusion. Coinsertion of GP64 with an F-like protein (Ac23) from group I virus led to efficient rescue of an F-null group II virus. In summary, these recombinant viruses and their entry modes are considered to resemble an evolutionary event of the acquisition of GP64 by an ancestral group I virus and subsequent adaptive inactivation of the original F protein. The study described here provides the first experimental evidence to support the hypothesis of the evolution of baculovirus EFPs.