Cleavage of Stau2 by 3C protease promotes EV-A71 replication.
Humans
Virus Replication
Enterovirus A, Human
/ physiology
RNA-Binding Proteins
/ metabolism
3C Viral Proteases
/ metabolism
Viral Proteins
/ metabolism
Cysteine Endopeptidases
/ metabolism
Host-Pathogen Interactions
Immunoprecipitation
Enterovirus Infections
/ virology
HEK293 Cells
Protein Binding
Nerve Tissue Proteins
3C protease
Cleavage
EV-A71
Stau2
Journal
Virology journal
ISSN: 1743-422X
Titre abrégé: Virol J
Pays: England
ID NLM: 101231645
Informations de publication
Date de publication:
13 Sep 2024
13 Sep 2024
Historique:
received:
01
08
2024
accepted:
04
09
2024
medline:
14
9
2024
pubmed:
14
9
2024
entrez:
13
9
2024
Statut:
epublish
Résumé
Enterovirus A71 (EV-A71), as a neurotropic virus, mainly affects infants and young children under the age of 5. EV-A71 infection causes hand-foot-mouth disease and herpetic angina, and even life-threatening neurological complications. However, the molecular mechanism by which EV-A71 induces nervous system damage remains elusive. The viral protease 3C plays an important role during EV-A71 infection and is also a key intersection of virus-host interactions. Previously, we used yeast two-hybrid to screen out the host protein Double-stranded RNA-binding protein Staufen homolog 2 (Stau2), an important member involved in neuronal mRNA transport, potentially interacts with 3C. We used coimmunoprecipitation (Co-IP) and immunofluorescence assay (IFA) to confirm that EV-A71 3C interacts with Stau2. By constructing the mutant of Stau2, we found the specific site where the 3C protease cleaves Stau2. Detection of VP1 protein using Western blotting characterized EV-A71 viral replication, and overexpression or knockdown of Stau2 exhibited effects on EV-A71 replication. The effect of different cleavage products on EV-A71 replication was demonstrated by constructing Stau2 truncates. In this study, we found that EV-A71 3C interacts with Stau2. Stau2 is cleaved by 3C at the Q507-G508 site. Overexpression of Stau2 promotes EV-A71 VP1 protein expression, whereas depletion of Stau2 by small interfering RNA inhibits EV-A71 replication. Stau2 is essential for EV-A71 replication, and the product of Stau2 cleavage by 3C, 508-570 aa, has activity that promotes EV-A71 replication. In addition, we found that mouse Stau2 is also cleaved by EV-A71 3C at the same site. Our research provides an example for EV-A71-host interaction, enriching key targets of host factors that contribute to viral replication.
Sections du résumé
BACKGROUND
BACKGROUND
Enterovirus A71 (EV-A71), as a neurotropic virus, mainly affects infants and young children under the age of 5. EV-A71 infection causes hand-foot-mouth disease and herpetic angina, and even life-threatening neurological complications. However, the molecular mechanism by which EV-A71 induces nervous system damage remains elusive. The viral protease 3C plays an important role during EV-A71 infection and is also a key intersection of virus-host interactions. Previously, we used yeast two-hybrid to screen out the host protein Double-stranded RNA-binding protein Staufen homolog 2 (Stau2), an important member involved in neuronal mRNA transport, potentially interacts with 3C.
METHODS
METHODS
We used coimmunoprecipitation (Co-IP) and immunofluorescence assay (IFA) to confirm that EV-A71 3C interacts with Stau2. By constructing the mutant of Stau2, we found the specific site where the 3C protease cleaves Stau2. Detection of VP1 protein using Western blotting characterized EV-A71 viral replication, and overexpression or knockdown of Stau2 exhibited effects on EV-A71 replication. The effect of different cleavage products on EV-A71 replication was demonstrated by constructing Stau2 truncates.
RESULTS
RESULTS
In this study, we found that EV-A71 3C interacts with Stau2. Stau2 is cleaved by 3C at the Q507-G508 site. Overexpression of Stau2 promotes EV-A71 VP1 protein expression, whereas depletion of Stau2 by small interfering RNA inhibits EV-A71 replication. Stau2 is essential for EV-A71 replication, and the product of Stau2 cleavage by 3C, 508-570 aa, has activity that promotes EV-A71 replication. In addition, we found that mouse Stau2 is also cleaved by EV-A71 3C at the same site.
CONCLUSIONS
CONCLUSIONS
Our research provides an example for EV-A71-host interaction, enriching key targets of host factors that contribute to viral replication.
Identifiants
pubmed: 39272111
doi: 10.1186/s12985-024-02489-6
pii: 10.1186/s12985-024-02489-6
doi:
Substances chimiques
RNA-Binding Proteins
0
3C Viral Proteases
EC 3.4.22.28
Viral Proteins
0
STAU2 protein, human
0
Cysteine Endopeptidases
EC 3.4.22.-
Nerve Tissue Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
216Subventions
Organisme : the National Natural Science Foundation of China
ID : 82302498
Organisme : the Key International Cooperation Project of the National Key Research and Development Program of China
ID : 2018YFE0107600
Informations de copyright
© 2024. The Author(s).
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