miR-142-5p Disrupts Neuronal Morphogenesis Underlying Porcine Hemagglutinating Encephalomyelitis Virus Infection by Targeting Ulk1

Li, Zi; Lan, Yungang; Zhao, Kui; Lv, Xiaoling; Ding, Ning; Lu, Huijun; Zhang, Jing; Yue, Huiqing; Shi, Junchao; Song, Deguang; Gao, Feng; He, Wenqi

Post-transcriptional regulation of virus-induced host microRNAs significantly contributed to CNS dysfunction, which suggested that the combination of multiple microRNAs may have had therapeutic potential in viral nerve disease. Earlier research showed that Ulk1 is required for endocytosis in response to NGF/TrkA complexes (Pelkmans et al., 2005; Zhou et al., 2007; Lee and Tournier, 2011) , and PHEV used the endo-/exocytosis for transsynaptic transfer (Li et al., 2013) . In general, endocytosis and intracellular trafficking of NGF/TrkA complex is necessary for a successful NGF signal transduction process to facilitate neurite outgrowth and a hallmark of neuron differentiation (Zhang et al., 2000) . In this paper, we found that miR-142-5p disrupts neuronal morphogenesis underlying PHEV infection by targeting Ulk1, whether the molecular mechanism is associated with endocytosis is still unknown. It was well known that NGF/TrkA complexes are endocytosed into Rab5a-positive early endosomes, and require inactivation of Rab5a to block early endosome fusion via RabGAP5 (Liu et al., 2007; Toda et al., 2008) . Thus, we proposed that miR-142-5p-mediated Ulk1 repression acted locally at individual neutrites and/or intracellular membranous structures, which contributed to NGF signaling and transsynaptic communication of the neurotropic virus mainly via the vesicle-mediated secretory pathway. Future work is needed to obtain insights into the fate of the Ulk1-mediated pathway processes in regulating diverse downstream signaling events during PHEV infection. However, more work in this area is likely to be discovered.