Exogenous expression of both matrix protein and glycoprotein facilitates infectious viral particle production of Borna disease virus 1
Exogenous expression of both matrix protein and glycoprotein facilitates infectious viral particle production of Borna disease virus 1
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DOI：
10.1099/jgv.0.001767
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发表时间：
2022-01-01
影响因子：
3.8
通讯作者：
Tomonaga, Keizo
中科院分区：
文献类型：
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作者：
Kanda, Takehiro;Sakai, Madoka;Tomonaga, Keizo
博尔纳病病毒1（BoDV- 1）是一种非节段负链RNA病毒，其特征在于在细胞核中持续感染和后代病毒体的低产量。该特征不仅阻碍了从感染的细胞中收获感染性病毒颗粒，而且阻碍了通过反向遗传学拯救高滴度的重组BoDV- 1（rBoDV- 1）。在这里，我们证明了作为病毒脂质包膜成分的基质蛋白（M）和糖蛋白（G）的外源表达显著促进了感染性颗粒的形成和BoDV- 1的繁殖，而不影响其病毒RNA的合成。此外，通过反向遗传学用N、P和L辅助质粒同时转染M和G表达质粒显著提高了rBoDV- 1的拯救效率。另一方面，我们还表明，M的过表达诱导明显的细胞毒性类似于其他单负病毒。结合我们最近的报告显示G的过量表达诱导不成熟G的异常积累，不成熟G是宿主先天免疫应答的潜在刺激物，可以想象BoDV- 1可能抑制M和G的过量表达以减少细胞病变效应，从而导致持续感染的维持。我们的研究结果不仅有助于建立一种有效的方法来回收高滴度的BoDV- 1，而且有助于理解持续感染BoDV- 1的独特机制。
Borna disease virus 1 (BoDV- 1) is a non-segmented, negative-strand RNA virus that is characterized by persistent infection in the nucleus and low production of progeny virions. This feature impedes not only the harvesting of infectious viral particles from infected cells but also the rescue of high titres of recombinant BoDV- 1 (rBoDV- 1) by reverse genetics. Here, we dem-onstrate that exogenous expression of both matrix protein (M) and glycoprotein (G), which are constituents of the viral lipid envelope, significantly facilitates the formation of infectious particles and propagation of BoDV- 1 without affecting its viral RNA synthesis. Furthermore, simultaneous transfection of M and G expression plasmids with N, P and L helper plasmids by reverse genetics drastically enhances the rescue efficiency of rBoDV- 1. On the other hand, we also show that overexpression of M induces obvious cytotoxicity similar to that of other Mononegaviruses. Together with our recent report showing that excess expression of G induces aberrant accumulation of immature G, a potential stimulator of the host innate immune response, it is conceivable that BoDV- 1 may suppress excess expression of M and G to reduce the cytopathic effect, thereby leading to main-tenance of persistent infection. Our results contribute not only to the establishment of an efficient method to recover high -titre BoDV- 1 but also to understanding the unique mechanism of persistent BoDV- 1 infection.