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

In previous studies, PHEV has been suggested to spread within and among nerve cells via microtubules and intermediate filaments (Hara et al., 2009) . Unexpectedly, we found that the spreading, stretching and arranging of neurons in PHEV-infected mice were disordered ( Figure 3A) . Moreover, primary cortical neurons had significantly shortened axon elongations upon PHEV infection at 8 days post-infection (dpi) (Figure 3B , upper panels). The presence of miR-142-5p in axons suggested that this microRNA might be involved in the regulation of embryonic cortical neuron morphology in response to PHEV in vivo and in vitro. To investigate this possible function, we examined the effects of modulating miR-142-5p activity on cortical neuron morphology. Representative images showed that both control neurons and inhibitor-transfected neurons ( Figure 3B ) mostly grew with two main axons that extended over a long distance, but significantly decreased axon elongation in neurons was detected when miR-142-5p was overexpressed ( Figure 3B , lower panels). We also measured the average length of the longest axon for each of the transfection categories, and quantitative analyses of these phenotypes were summarized in histograms ( Figure 3C) . These findings suggested that miR-142-5p overexpression negatively affect cortical neuron development and morphogenesis. We concluded that miR-142-5p acted as a negative regulator of axon elongation in primary cortical neurons and was involved in the regulation of axon development and/or functional responses to PHEV.