miR-142-5p Disrupts Neuronal Morphogenesis Underlying Porcine Hemagglutinating Encephalomyelitis Virus Infection by Targeting Ulk1
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 neu...
Main Authors: | , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Frontiers Media S.A.
2017-05-01
|
Series: | Frontiers in Cellular and Infection Microbiology |
Subjects: | |
Online Access: | http://journal.frontiersin.org/article/10.3389/fcimb.2017.00155/full |
id |
doaj-cbfb0ad6d3e64cec9b901db9f4399bea |
---|---|
record_format |
Article |
spelling |
doaj-cbfb0ad6d3e64cec9b901db9f4399bea2020-11-24T23:38:41ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882017-05-01710.3389/fcimb.2017.00155255912miR-142-5p Disrupts Neuronal Morphogenesis Underlying Porcine Hemagglutinating Encephalomyelitis Virus Infection by Targeting Ulk1Zi Li0Yungang Lan1Kui Zhao2Xiaoling Lv3Ning Ding4Huijun Lu5Jing Zhang6Huiqing Yue7Junchao Shi8Deguang Song9Feng Gao10Wenqi He11Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin UniversityChangchun, ChinaKey Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin UniversityChangchun, ChinaKey Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin UniversityChangchun, ChinaKey Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin UniversityChangchun, ChinaKey Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin UniversityChangchun, ChinaKey Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, Jilin UniversityChangchun, ChinaKey Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin UniversityChangchun, ChinaKey Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin UniversityChangchun, ChinaKey Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin UniversityChangchun, ChinaKey Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin UniversityChangchun, ChinaKey Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin UniversityChangchun, ChinaKey Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin UniversityChangchun, ChinaPorcine 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 demonstrated that the abnormal neuronal morphogenesis underlying PHEV infection was mainly caused by functional mRNA repression of the miR-142-5p target Ulk1. Our data revealed that PHEV adapted to use spatiotemporal control of host microRNAs to invade CNS, and provided new insights into the virus-associated neurological dysfunction microenvironment.http://journal.frontiersin.org/article/10.3389/fcimb.2017.00155/fullPorcine hemagglutinating encephalomyelitis virusneurotropic virusmiR-142-5pUlk1neuronal morphogenesis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Zi Li Yungang Lan Kui Zhao Xiaoling Lv Ning Ding Huijun Lu Jing Zhang Huiqing Yue Junchao Shi Deguang Song Feng Gao Wenqi He |
spellingShingle |
Zi Li Yungang Lan Kui Zhao Xiaoling Lv Ning Ding Huijun Lu Jing Zhang Huiqing Yue Junchao Shi Deguang Song Feng Gao Wenqi He miR-142-5p Disrupts Neuronal Morphogenesis Underlying Porcine Hemagglutinating Encephalomyelitis Virus Infection by Targeting Ulk1 Frontiers in Cellular and Infection Microbiology Porcine hemagglutinating encephalomyelitis virus neurotropic virus miR-142-5p Ulk1 neuronal morphogenesis |
author_facet |
Zi Li Yungang Lan Kui Zhao Xiaoling Lv Ning Ding Huijun Lu Jing Zhang Huiqing Yue Junchao Shi Deguang Song Feng Gao Wenqi He |
author_sort |
Zi Li |
title |
miR-142-5p Disrupts Neuronal Morphogenesis Underlying Porcine Hemagglutinating Encephalomyelitis Virus Infection by Targeting Ulk1 |
title_short |
miR-142-5p Disrupts Neuronal Morphogenesis Underlying Porcine Hemagglutinating Encephalomyelitis Virus Infection by Targeting Ulk1 |
title_full |
miR-142-5p Disrupts Neuronal Morphogenesis Underlying Porcine Hemagglutinating Encephalomyelitis Virus Infection by Targeting Ulk1 |
title_fullStr |
miR-142-5p Disrupts Neuronal Morphogenesis Underlying Porcine Hemagglutinating Encephalomyelitis Virus Infection by Targeting Ulk1 |
title_full_unstemmed |
miR-142-5p Disrupts Neuronal Morphogenesis Underlying Porcine Hemagglutinating Encephalomyelitis Virus Infection by Targeting Ulk1 |
title_sort |
mir-142-5p disrupts neuronal morphogenesis underlying porcine hemagglutinating encephalomyelitis virus infection by targeting ulk1 |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Cellular and Infection Microbiology |
issn |
2235-2988 |
publishDate |
2017-05-01 |
description |
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 demonstrated that the abnormal neuronal morphogenesis underlying PHEV infection was mainly caused by functional mRNA repression of the miR-142-5p target Ulk1. Our data revealed that PHEV adapted to use spatiotemporal control of host microRNAs to invade CNS, and provided new insights into the virus-associated neurological dysfunction microenvironment. |
topic |
Porcine hemagglutinating encephalomyelitis virus neurotropic virus miR-142-5p Ulk1 neuronal morphogenesis |
url |
http://journal.frontiersin.org/article/10.3389/fcimb.2017.00155/full |
work_keys_str_mv |
AT zili mir1425pdisruptsneuronalmorphogenesisunderlyingporcinehemagglutinatingencephalomyelitisvirusinfectionbytargetingulk1 AT yunganglan mir1425pdisruptsneuronalmorphogenesisunderlyingporcinehemagglutinatingencephalomyelitisvirusinfectionbytargetingulk1 AT kuizhao mir1425pdisruptsneuronalmorphogenesisunderlyingporcinehemagglutinatingencephalomyelitisvirusinfectionbytargetingulk1 AT xiaolinglv mir1425pdisruptsneuronalmorphogenesisunderlyingporcinehemagglutinatingencephalomyelitisvirusinfectionbytargetingulk1 AT ningding mir1425pdisruptsneuronalmorphogenesisunderlyingporcinehemagglutinatingencephalomyelitisvirusinfectionbytargetingulk1 AT huijunlu mir1425pdisruptsneuronalmorphogenesisunderlyingporcinehemagglutinatingencephalomyelitisvirusinfectionbytargetingulk1 AT jingzhang mir1425pdisruptsneuronalmorphogenesisunderlyingporcinehemagglutinatingencephalomyelitisvirusinfectionbytargetingulk1 AT huiqingyue mir1425pdisruptsneuronalmorphogenesisunderlyingporcinehemagglutinatingencephalomyelitisvirusinfectionbytargetingulk1 AT junchaoshi mir1425pdisruptsneuronalmorphogenesisunderlyingporcinehemagglutinatingencephalomyelitisvirusinfectionbytargetingulk1 AT deguangsong mir1425pdisruptsneuronalmorphogenesisunderlyingporcinehemagglutinatingencephalomyelitisvirusinfectionbytargetingulk1 AT fenggao mir1425pdisruptsneuronalmorphogenesisunderlyingporcinehemagglutinatingencephalomyelitisvirusinfectionbytargetingulk1 AT wenqihe mir1425pdisruptsneuronalmorphogenesisunderlyingporcinehemagglutinatingencephalomyelitisvirusinfectionbytargetingulk1 |
_version_ |
1725516184352194560 |