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

Frontiers in Cellular and Infection Microbiology
Zi LiWenqi He

Abstract

Porcine hemagglutinating encephalomyelitis virus (PHEV) invades the central nervous system (CNS) and causes neurodegenerative disease in suckling piglets, but the understanding of its neuropathogenicity for neurological dysfunction remains limited. Here, we report that miR-142-5p is localized to neurons and negatively regulates neuronal morphogenesis in porcine hemagglutinating encephalomyelitis (PHE). This phenotype was mediated by miR-142-5p inhibition of an mRNA encoding unc-51-like-kinase1 (Ulk1), which controls axon outgrowth and dendrite formation. Modulating miR-142-5p activity by microRNA mimics or inhibitors induced neurodegeneration, including stunted axon elongation, unstable dendritic spine formation, and irregular swelling and disconnection in neurites. Relieving Ulk1 mRNA repression in primary cortical neurons by miR-142-5p antagomirs or replication-deficient adenoviruses encoding Ulk1 (Ad5-Ulk1), which improved rescue of nerve injury, restricted viral replication, and increased survival rate in mice underlying PHEV infection. In contrast, disrupting Ulk1 in RNAi-expressing neurons mostly led to significantly shortened axon elongation and/or an abnormally large number of branched dendrites. Taken together, we demo...Continue Reading

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Citations

Mar 16, 2019·Frontiers in Veterinary Science·Juan Carlos Mora-DíazLuis Gabriel Giménez-Lirola
Mar 26, 2021·Journal of Virology·Juan Carlos Mora-DíazLuis G Giménez-Lirola

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Datasets Mentioned

BETA
MIMAT0000154
AY078417.1

Methods Mentioned

BETA
transfection
transfections
PCR
Assay
Electrophoretic
electrophoretic mobility shift assay

Software Mentioned

Image J
ImageJ
GraphPad Prism

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