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淋巴细胞性脉络丛脑膜炎病毒MX株在持续感染期间的细胞间传播及其对细胞迁移的影响。

Cell-to-cell transmission of lymphocytic choriomeningitis virus MX strain during persistent infection and its influence on cell migration.

作者信息

Labudová M, Čiampor F, Pastoreková S, Pastorek J

出版信息

Acta Virol. 2018;62(4):424-434. doi: 10.4149/av_2018_411.

DOI:10.4149/av_2018_411
PMID:30472873
Abstract

Lymphocytic choriomeningitis virus (LCMV) can establish in its host a persistent infection, without any prominent symptoms. Even during this infection, when the infectious virions are not released, the virus still disseminates effectively. A very effective and fast way of infection of neighboring cells utilized by many viruses is cell-to-cell transmission. Viruses use different ways of cell-to-cell spread through the extracellular space or by intracellular means through different protrusions. We have found that LCMV strain MX may use three different types of cell-to-cell transport. Firstly, similar to vaccinia virus, it can use actin to propel the virus towards the neighboring cell. Secondly, virus can travel through the intracellular space inside the tunneling nanotubes, that connect the cells even at longer distances and thirdly, the virus may travel on the surface of the membrane of different protrusions connecting two cells. We have also proved that the cells infected by MX strain of LCMV migrate faster than the uninfected cells or cells infected with a different LCMV strain. In accordance with faster migration, the infected cells form more lamellipodia with high expression of keratin 1. In this work, we have introduced three types of cell-to-cell transmission utilized by strain MX of LCMV and showed that even if the cells are not in tight connection, the virus forces them to migrate faster to join the nearest cell. As we show in this work, the virus may use more than one strategy to move to another cell, while each strategy can substitute another. These ways of transmission are very fast and effective and may have a serious impact on the host. Moreover, targeting the cell-to-cell spread, by inhibiting for instance GTPase dynamin, could be an effective way of virus elimination. Keywords: lymphocytic choriomeningitis virus; transmission; migration; keratin 1; nucleoprotein.

摘要

淋巴细胞性脉络丛脑膜炎病毒(LCMV)可在其宿主中建立持续性感染,且无任何明显症状。即使在这种感染期间,当感染性病毒粒子未释放时,病毒仍能有效传播。许多病毒利用的一种非常有效且快速的感染邻近细胞的方式是细胞间传播。病毒通过细胞外空间或通过不同突起的细胞内方式采用不同的细胞间传播途径。我们发现LCMV毒株MX可能使用三种不同类型的细胞间运输方式。首先,与痘苗病毒类似,它可以利用肌动蛋白将病毒推向邻近细胞。其次,病毒可以通过隧道纳米管内的细胞内空间传播,隧道纳米管甚至可以在较长距离连接细胞,第三,病毒可能在连接两个细胞的不同突起的膜表面移动。我们还证明,被LCMV的MX毒株感染的细胞比未感染的细胞或被不同LCMV毒株感染的细胞迁移得更快。与更快的迁移一致,被感染的细胞形成更多具有角蛋白1高表达的片状伪足。在这项工作中,我们介绍了LCMV的MX毒株利用的三种细胞间传播类型,并表明即使细胞没有紧密连接,病毒也会迫使它们更快迁移以与最近的细胞结合。正如我们在这项工作中所展示的,病毒可能使用不止一种策略移动到另一个细胞,而每种策略都可以替代另一种。这些传播方式非常快速有效,可能会对宿主产生严重影响。此外,通过抑制例如GTPase发动蛋白来靶向细胞间传播可能是消除病毒的有效方法。关键词:淋巴细胞性脉络丛脑膜炎病毒;传播;迁移;角蛋白1;核蛋白

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