Institute of Animal Quarantine, Chinese Academy of Inspection and Quarantine, Beijing 100029, People's Republic of China.
Virology. 2013 Mar 1;437(1):28-38. doi: 10.1016/j.virol.2012.12.011. Epub 2013 Jan 11.
Peste des petits ruminants virus (PPRV) is an important pathogen that seriously influences the productivity of small ruminants worldwide. Although PPRV is known to induce apoptosis in infected cells, the interaction between PPRV and permissive cells requires further elucidation. Here, we provide the first evidence that PPRV infection triggered autophagy in Vero cells based on the appearance of abundant double- and single-membrane vesicles, the accumulation of LC3 fluorescent puncta, the enhancement of LC3-I/-II conversion, and autophagic flux. We further demonstrated that induction of autophagy with rapamycin significantly increased PPRV progeny yield and nucleocapsid (N) protein expression, while inhibition of autophagy with siRNA targeting ATG7 resulted in diametrically opposite results. Our data indicate that PPRV exploits the autophagy machinery to facilitate its own replication in host cells, thus the production efficiency of live attenuated PPRV vaccines may be improved by targeting the autophagic pathway.
小反刍兽疫病毒(PPRV)是一种重要的病原体,它严重影响了全球小反刍动物的生产力。虽然已知 PPRV 可诱导感染细胞凋亡,但 PPRV 与允许细胞之间的相互作用需要进一步阐明。在这里,我们首次提供了证据,表明 PPRV 感染在 Vero 细胞中引发了自噬,其特征是出现大量双层和单层囊泡、LC3 荧光斑点的积累、LC3-I/-II 转化的增强和自噬流。我们进一步证明,用雷帕霉素诱导自噬可显著增加 PPRV 后代的产量和核衣壳(N)蛋白的表达,而用靶向 ATG7 的 siRNA 抑制自噬则产生截然相反的结果。我们的数据表明,PPRV 利用自噬机制来促进其在宿主细胞中的复制,因此通过靶向自噬途径可以提高活减毒 PPRV 疫苗的生产效率。