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Cleavage of Stau2 by 3C protease promotes EV-A71 replication.
- Source :
-
Virology journal [Virol J] 2024 Sep 13; Vol. 21 (1), pp. 216. Date of Electronic Publication: 2024 Sep 13. - Publication Year :
- 2024
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Abstract
- 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.<br />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.<br />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.<br />Conclusions: Our research provides an example for EV-A71-host interaction, enriching key targets of host factors that contribute to viral replication.<br /> (© 2024. The Author(s).)
- Subjects :
- Humans
Cysteine Endopeptidases metabolism
Cysteine Endopeptidases genetics
Host-Pathogen Interactions
Immunoprecipitation
Enterovirus Infections virology
Enterovirus Infections metabolism
HEK293 Cells
Protein Binding
Nerve Tissue Proteins
Virus Replication
Enterovirus A, Human physiology
Enterovirus A, Human genetics
RNA-Binding Proteins metabolism
RNA-Binding Proteins genetics
3C Viral Proteases metabolism
Viral Proteins metabolism
Viral Proteins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1743-422X
- Volume :
- 21
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Virology journal
- Publication Type :
- Academic Journal
- Accession number :
- 39272111
- Full Text :
- https://doi.org/10.1186/s12985-024-02489-6