Yu Wanting, Sun Yuao, He Qing, Sun Chaoying, Dong Tian, Zhang Luhua, Zhan Yang, Wang Naidong, Yang Yi, Sun Yujie
Biomedical Pioneer Innovation Center (BIOPIC), School of Life Sciences, Peking University, Beijing 100871, China.
School of Future Technology, Peking University, Beijing 100871, China.
Vet Sci. 2021 Nov 10;8(11):272. doi: 10.3390/vetsci8110272.
Porcine circovirus 2 (PCV2), considered one of the most globally important porcine pathogens, causes postweaning multisystemic wasting syndrome (PMWS). This virus is localized in the mitochondria in pigs with PMWS. Here, we identified, for the first time, a mitochondrial localization signal (MLS) in the PCV2 capsid protein (Cap) at the N-terminus. PK-15 cells showed colocalization of the MLS-EGFP fusion protein with mitochondria. Since the PCV2 Cap also contained a nuclear localization signal (NLS) that mediated entry into the nucleus, we inferred that the subcellular localization of the PCV2 Cap is inherently complex and dependent on the viral life cycle. Furthermore, we also determined that deletion of the MLS attenuated Cap-induced apoptosis. More importantly, the MLS was essential for PCV2 replication, as absence of the MLS resulted in failure of virus rescue from cells infected with infectious clone DNA. In conclusion, the MLS of the PCV2 Cap plays critical roles in Cap-induced apoptosis, and MLS deletion of Cap is lethal for virus rescue.
猪圆环病毒2型（PCV2）被认为是全球最重要的猪病原体之一，可引起断奶后多系统消耗综合征（PMWS）。该病毒定位于患有PMWS的猪的线粒体中。在此，我们首次在PCV2衣壳蛋白（Cap）的N端鉴定出一个线粒体定位信号（MLS）。PK - 15细胞显示MLS - EGFP融合蛋白与线粒体共定位。由于PCV2 Cap还含有介导进入细胞核的核定位信号（NLS），我们推断PCV2 Cap的亚细胞定位本质上是复杂的，并且依赖于病毒生命周期。此外，我们还确定删除MLS可减弱Cap诱导的细胞凋亡。更重要的是，MLS对PCV2复制至关重要，因为缺少MLS会导致无法从感染感染性克隆DNA的细胞中拯救出病毒。总之，PCV2 Cap的MLS在Cap诱导的细胞凋亡中起关键作用，并且Cap的MLS缺失对病毒拯救是致命的。
