Dual control of tick-borne encephalitis virus replication by autophagy in mouse macrophages
Dual control of tick-borne encephalitis virus replication by autophagy in mouse macrophages
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DOI：
10.1016/j.virusres.2022.198778
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发表时间：
2022-04-21
期刊：
影响因子：
5
通讯作者：
Lieskovska, Jaroslava
中科院分区：
文献类型：
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作者：
Berankova, Zuzana;Kopecky, Jan;Lieskovska, Jaroslava
自噬是一种溶酶体降解途径，负责回收胞浆蛋白和细胞器，也是宿主细胞抵御病毒感染的一种天然防御机制。虽然许多病毒已经进化出机制来对抗自噬途径的抗病毒作用，但另一些病毒则颠覆了自噬以促进复制。对于黄病毒，自噬在病毒复制中的积极和消极作用都已有报道。自噬和壁虱传播的脑炎病毒(TBEV)在天然免疫细胞中的相互作用在很大程度上是未知的。在这里，我们报道了使用TBEV Hypr株在小鼠巨噬细胞系PMJ2-R中的自噬和TBEV复制之间的关系。首先，我们研究了Hypr感染对自噬途径的影响。我们在Hypr感染的细胞中检测到自噬标记物LC3-II有轻微和暂时的增加。在自噬相关基因5(ATG5)敲除细胞(ShAtg5)中评价自噬在TBEV复制中的作用。我们的结果表明，在Hypr感染的早期阶段，病毒滴度升高，而后来，在72HPI时，shAtg5细胞的病毒滴度与对照组相比有所下降。此外，在感染早期的shAtg5细胞中观察到较多的病毒阳性细胞，并与病毒进入的增强有关。最后，我们发现Hypr感染的shAtg5细胞在48HPI和72HPI时产生的干扰素-β比对照组增加，这意味着自噬限制了感染TBEV的巨噬细胞产生干扰素的数量。总之，在小鼠巨噬细胞中，TBEV的复制是由自噬以时间依赖的方式控制的，在感染期间具有暂时的抗病毒作用和亲病毒作用。我们的研究指出，在控制TBEV感染时，自噬机制在病毒进入和干扰素-β的产生水平上涉及到微妙和复杂的参与。
Autophagy is a lysosomal degradative pathway responsible for recycling cytosolic proteins and organelles and also functions as an innate defense mechanism that host cells use against viral infection. While many viruses have evolved mechanisms to antagonize the antiviral effects of the autophagy pathway, others subvert autophagy to facilitate replication. For flaviviruses, both the positive and negative role of autophagy in virus replication has been reported. The interplay between autophagy and tick-borne encephalitis virus (TBEV) in innate immune cells is largely unknown. Here we report the relationship between an autophagy and TBEV replication in mouse macrophage cell line PMJ2-R using Hypr strain of TBEV. First, we examined the effect of Hypr infection on the autophagy pathway. We detected a mild and a temporary increase of autophagy marker LC3-II in Hypr-infected cells. The role of autophagy in TBEV replication was evaluated in autophagy related gene 5 (Atg5) knockdown cells (shAtg5). Our results showed that during an early stage of Hypr infection the viral titers were increased, while later on, at 72 hpi, the titers have declined in shAtg5 cells compared to control. Moreover, the higher number of virus-positive cells was observed in shAtg5 cells in early stage of infection and correlated with enhanced virus entry. Finally, we found an increased production of IFN-beta in Hypr-infected shAtg5 cells in comparison to control at 48 and 72 hpi implicating that autophagy restricts the amount of IFN produced by TBEV-infected macrophages. To conclude, in mouse macrophages TBEV replication is controlled by autophagy in time dependent manner, having temporally an antiviral and then a pro-viral role during infection. Our study points out to a delicate and complex involvement of autophagy machinery at level of virus entry and IFN-beta production when controlling TBEV infection.