Chen Deyan, Feng Chunhong, Tian Xiaoyan, Zheng Nan, Wu Zhiwei
Center for Public Health Research, Medical School, Nanjing University, Nanjing, China.
State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing, China.
Front Immunol. 2018 Jun 5;9:1268. doi: 10.3389/fimmu.2018.01268. eCollection 2018.
The promyelocytic leukemia (PML) protein, also known as TRIM19, functions as a major organizer of PML nuclear bodies (NBs) in most mammalian cells and plays important roles in antiviral activities against both DNA and RNA viruses. In this study, we found that the downregulation of PML rendered HeLa cells more susceptible to infection by enterovirus 71 (EV71), and the overexpression of the PMLIII or PMLIV isoforms inhibited viral protein expression and resulted in viral titers that were 2-3 log units lower than those in the control. Using short interfering RNAs, the downregulation of either the PMLIII or PMLIV isoform increased both viral protein VP1 expression and viral production. The PML repression of EV71 replication was partially mediated by the inhibition of autophagy, and PML deficiency triggered autophagy. Furthermore, the EV71 infection resulted in a reduction in PML independent of the proteasome pathway. Instead, PML degradation was mediated by virus protease 3C. In conclusion, PML contributes to a cellular antiviral effect by inhibiting autophagy, which is countered by a disruption of promyelocytic leukemia protein-nuclear bodies mediated by viral protease 3C.
早幼粒细胞白血病（PML）蛋白，也称为TRIM19，在大多数哺乳动物细胞中作为PML核体（NBs）的主要组织者发挥作用，并在针对DNA和RNA病毒的抗病毒活性中发挥重要作用。在本研究中，我们发现PML的下调使HeLa细胞更容易受到肠道病毒71型（EV71）的感染，而PMLIII或PMLIV亚型的过表达抑制了病毒蛋白表达，并导致病毒滴度比对照低2-3个对数单位。使用小干扰RNA，PMLIII或PMLIV亚型的下调均增加了病毒蛋白VP1的表达和病毒产生。PML对EV71复制的抑制部分是通过抑制自噬介导的，而PML缺乏会引发自噬。此外，EV71感染导致PML减少，且不依赖于蛋白酶体途径。相反，PML的降解是由病毒蛋白酶3C介导的。总之，PML通过抑制自噬发挥细胞抗病毒作用，而病毒蛋白酶3C介导的早幼粒细胞白血病蛋白-核体破坏会抵消这种作用。
