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About:
Porcine Hemagglutinating Encephalomyelitis Virus Enters Neuro-2a Cells via Clathrin-Mediated Endocytosis in a Rab5-, Cholesterol-, and pH-Dependent Manner
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An Entity of Type :
schema:ScholarlyArticle
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wasabi.inria.fr
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Type:
Academic Article
research paper
schema:ScholarlyArticle
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type
Academic Article
research paper
schema:ScholarlyArticle
isDefinedBy
Covid-on-the-Web dataset
has title
Porcine Hemagglutinating Encephalomyelitis Virus Enters Neuro-2a Cells via Clathrin-Mediated Endocytosis in a Rab5-, Cholesterol-, and pH-Dependent Manner
Creator
Zhang, Jing
Gao, Feng
He, Wenqi
Lan, Yungang
Lu, Huijun
Song, Deguang
Zhao, Kui
Li, Zi
Lv, Xiaoling
Guan, Jiyu
Hu, Shiyu
Shi, Junchao
Yang, Yawen
Li, Citation
Pfeiffer, Julie
Source
Medline; PMC
abstract
Porcine hemagglutinating encephalomyelitis virus (PHEV) is a highly neurovirulent coronavirus that invades the central nervous system (CNS) in piglets. Although important progress has been made toward understanding the biology of PHEV, many aspects of its life cycle remain obscure. Here we dissected the molecular mechanism underlying cellular entry and intracellular trafficking of PHEV in mouse neuroblastoma (Neuro-2a) cells. We first performed a thin-section transmission electron microscopy (TEM) assay to characterize the kinetics of PHEV, and we found that viral entry and transfer occur via membranous coating-mediated endo- and exocytosis. To verify the roles of distinct endocytic pathways, systematic approaches were used, including pharmacological inhibition, RNA interference, confocal microscopy analysis, use of fluorescently labeled virus particles, and overexpression of a dominant negative (DN) mutant. Quantification of infected cells showed that PHEV enters cells by clathrin-mediated endocytosis (CME) and that low pH, dynamin, cholesterol, and Eps15 are indispensably involved in this process. Intriguingly, PHEV invasion leads to rapid actin rearrangement, suggesting that the intactness and dynamics of the actin cytoskeleton are positively correlated with viral endocytosis. We next investigated the trafficking of internalized PHEV and found that Rab5- and Rab7-dependent pathways are required for the initiation of a productive infection. Furthermore, a GTPase activation assay suggested that endogenous Rab5 is activated by PHEV and is crucial for viral progression. Our findings demonstrate that PHEV hijacks the CME and endosomal system of the host to enter and traffic within neural cells, providing new insights into PHEV pathogenesis and guidance for antiviral drug design. IMPORTANCE Porcine hemagglutinating encephalomyelitis virus (PHEV), a nonsegmented, positive-sense, single-stranded RNA coronavirus, invades the central nervous system (CNS) and causes neurological dysfunction. Neural cells are its targets for viral progression. However, the detailed mechanism underlying PHEV entry and trafficking remains unknown. PHEV is the etiological agent of porcine hemagglutinating encephalomyelitis, which is an acute and highly contagious disease that causes numerous deaths in suckling piglets and enormous economic losses in China. Understanding the viral entry pathway will not only advance our knowledge of PHEV infection and pathogenesis but also open new approaches to the development of novel therapeutic strategies. Therefore, we employed systematic approaches to dissect the internalization and intracellular trafficking mechanism of PHEV in Neuro-2a cells. This is the first report to describe the process of PHEV entry into nerve cells via clathrin-mediated endocytosis in a dynamin-, cholesterol-, and pH-dependent manner that requires Rab5 and Rab7.
has issue date
2017-11-14
(
xsd:dateTime
)
bibo:doi
10.1128/jvi.01083-17
bibo:pmid
28956766
has license
cc-by
sha1sum (hex)
d1ab379487b829f2a3d3f78f27a427f2dd87deda
schema:url
https://doi.org/10.1128/jvi.01083-17
resource representing a document's title
Porcine Hemagglutinating Encephalomyelitis Virus Enters Neuro-2a Cells via Clathrin-Mediated Endocytosis in a Rab5-, Cholesterol-, and pH-Dependent Manner
has PubMed Central identifier
PMC5686734
has PubMed identifier
28956766
schema:publication
J Virol
resource representing a document's body
covid:d1ab379487b829f2a3d3f78f27a427f2dd87deda#body_text
is
schema:about
of
named entity 'membranous'
named entity 'highly'
named entity 'detailed'
named entity 'mechanism'
named entity 'losses'
named entity 'kinetics'
named entity 'cells'
named entity 'Journal'
named entity 'clathrin-mediated endocytosis'
named entity 'cholesterol'
named entity 'infection'
named entity 'mechanism'
named entity 'central nervous system (CNS)'
named entity 'clathrin-mediated endocytosis'
named entity 'Journal'
named entity 'viral'
named entity 'Rab'
named entity 'cellular'
named entity 'acute'
named entity 'Virus'
named entity 'REMAINS'
covid:arg/d1ab379487b829f2a3d3f78f27a427f2dd87deda
named entity 'RAB5'
named entity 'ACTIVATED'
named entity 'DISSECTED'
named entity 'CENTRAL NERVOUS SYSTEM'
named entity 'ENDOCYTOSIS'
named entity 'TO CHARACTERIZE'
named entity 'CONFOCAL MICROSCOPY'
named entity 'VIRAL'
named entity 'DEATHS'
named entity 'POSITIVE'
named entity 'NOVEL'
named entity 'RABS'
named entity 'ASM'
named entity 'CHOLESTEROL'
named entity 'PROGRESS'
named entity 'ORG'
named entity 'TARGETS'
named entity 'BUT'
named entity 'INSIGHTS'
named entity 'MEMBRANOUS'
named entity 'DECEMBER'
named entity 'DYNAMIN'
named entity 'CORONAVIRUS'
named entity 'MOLECULAR MECHANISM'
named entity 'CAUSES'
named entity 'REARRANGEMENT'
named entity 'CLATHRIN-MEDIATED ENDOCYTOSIS'
named entity 'INFECTION'
named entity 'CELLS'
named entity 'REQUIRED'
named entity 'KNOWLEDGE'
named entity 'QUANTIFICATION'
named entity 'ASSAY'
named entity 'INVASION'
named entity 'ACTIN CYTOSKELETON'
named entity 'EPS15'
named entity 'DETAILED'
named entity 'TRAFFICKING'
named entity 'PHARMACOLOGICAL'
named entity 'OPEN'
named entity 'DRUG DESIGN'
named entity 'INTACTNESS'
named entity 'NEURO-2A'
named entity 'HIGHLY CONTAGIOUS DISEASE'
named entity 'RNA INTERFERENCE'
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