PDF(Pubmed)
Abstract：
FeHV-1 is a member of the Herpesviridae family that is distributed worldwide and causes feline viral rhinotracheitis (FVR). Since its relationship with the autophagic process has not yet been elucidated, the aim of this work was to evaluate the autophagy mediated by FeHV-1 and to determine its proviral or antiviral role. Our data showed that autophagy is induced by FeHV-1 in a viral dose and time-dependent manner. Phenotypic changes in LC3/p62 axis (increase of LC3-II and degradation of p62) were detected from 12 h post infection using western blot and immuno-fluorescence assays. In a second step, by using late autophagy inhibitors and inducers, the possible proviral role of autophagy during FeHV-1 infection was investigating by assessing the effects of each chemical in terms of viral yield, cytotoxic effects, and expression of viral glycoproteins. Our findings suggest that late-stage autophagy inhibitors (bafilomycin and chloroquine) have a negative impact on viral replication. Interestingly, we observed an accumulation of gB, a viral protein, when cells were pretreated with bafilomycin, whereas the opposite effect was observed when an autophagy inducer was used. The importance of autophagy during FeHV-1 infection was further supported by the results obtained with ATG5 siRNA. In summary, this study demonstrates FeHV-1-mediated autophagy induction, its proviral role, and the negative impact of late autophagy inhibitors on viral replication.
摘要：
FeHV-1是疱疹病毒科的成员，分布在世界各地，并引起猫病毒性鼻支气管炎（FVR）。由于它与自噬过程的关系尚未阐明，这项工作的目的是评估FeHV-1介导的自噬,并确定其前病毒或抗病毒作用.我们的数据显示FeHV-1以病毒剂量和时间依赖性方式诱导自噬。使用蛋白质印迹和免疫荧光测定从感染后12小时检测到LC3/p62轴的表型变化(LC3-II的增加和p62的降解)。第二步,通过使用晚期自噬抑制剂和诱导剂，通过评估每种化学物质在病毒产量方面的作用，研究了自噬在FeHV-1感染期间可能的前病毒作用，细胞毒性作用，和病毒糖蛋白的表达。我们的研究结果表明，晚期自噬抑制剂（巴菲霉素和氯喹）对病毒复制有负面影响。有趣的是,我们观察到gB的积累，一种病毒蛋白，当细胞用巴弗洛霉素预处理时，而当使用自噬诱导剂时，观察到相反的效果。用ATG5siRNA获得的结果进一步支持了FeHV-1感染期间自噬的重要性。总之,这项研究证明了FeHV-1介导的自噬诱导，它的原作用，以及晚期自噬抑制剂对病毒复制的负面影响。
