Porcine Hemagglutinating Encephalomyelitis Virus Activation of the Integrin α5β1-FAK-Cofilin Pathway Causes Cytoskeletal Rearrangement To Promote Its Invasion of N2a Cells.
Actin Cytoskeleton
/ metabolism
Actin Depolymerizing Factors
/ metabolism
Animals
Betacoronavirus 1
/ metabolism
Cell Line
Coronavirus Infections
/ pathology
Focal Adhesion Kinase 1
/ metabolism
Integrin alpha5beta1
/ metabolism
Nerve Degeneration
/ veterinary
Swine
cdc42 GTP-Binding Protein
/ metabolism
p21-Activated Kinases
/ metabolism
cofilin
coronavirus
cytoskeletal rearrangement
integrin α5β1
neurotropic virus
porcine hemagglutinating encephalomyelitis virus
Journal
Journal of virology
ISSN: 1098-5514
Titre abrégé: J Virol
Pays: United States
ID NLM: 0113724
Informations de publication
Date de publication:
01 03 2019
01 03 2019
Historique:
received:
02
10
2018
accepted:
05
12
2018
pubmed:
14
12
2018
medline:
21
11
2019
entrez:
14
12
2018
Statut:
epublish
Résumé
Porcine hemagglutinating encephalomyelitis virus (PHEV) is a highly neurotropic virus that causes diffuse neuronal infection with neurological damage and high mortality. Virus-induced cytoskeletal dynamics are thought to be closely related to this type of nerve damage. Currently, the regulation pattern of the actin cytoskeleton and its molecular mechanism remain unclear when PHEV enters the host cells. Here, we demonstrate that entry of PHEV into N2a cells induces a biphasic remodeling of the actin cytoskeleton and a dynamic change in cofilin activity. Viral entry is affected by the disruption of actin kinetics or alteration of cofilin activity. PHEV binds to integrin α5β1 and then initiates the integrin α5β1-FAK signaling pathway, leading to virus-induced early cofilin phosphorylation and F-actin polymerization. Additionally, Ras-related C3 botulinum toxin substrate 1 (Rac1), cell division cycle 42 (Cdc42), and downstream regulatory gene p21-activated protein kinases (PAKs) are recruited as downstream mediators of PHEV-induced dynamic changes of the cofilin activity pathway. In conclusion, we demonstrate that PHEV utilizes the integrin α5β1-FAK-Rac1/Cdc42-PAK-LIMK-cofilin pathway to cause an actin cytoskeletal rearrangement to promote its own invasion, providing theoretical support for the development of PHEV pathogenic mechanisms and new antiviral targets.
Identifiants
pubmed: 30541856
pii: JVI.01736-18
doi: 10.1128/JVI.01736-18
pmc: PMC6384086
pii:
doi:
Substances chimiques
Actin Depolymerizing Factors
0
Integrin alpha5beta1
0
Focal Adhesion Kinase 1
EC 2.7.10.2
p21-Activated Kinases
EC 2.7.11.1
cdc42 GTP-Binding Protein
EC 3.6.5.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2019 American Society for Microbiology.
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