DEAD-box RNA helicase 21 interacts with the nucleocapsid protein and inhibits porcine deltacoronavirus infection through upregulation of interferon responses
6 affiliations
- 1College of Bioscience and Engineering, Jiangxi Agricultural University, Nanchang, China
- 2Institute of Pathogenic Microorganism, Jiangxi Agricultural University, Nanchang, China
- 3Jiangxi Provincial Key Laboratory for Animal Health, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang, China
- 4Key Laboratory of Veterinary Biological Engineering and Technology, Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, Nanjing, China
- 5Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, China
- 6College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang, China
Abstract
DEAD-box RNA helicase 21 (DDX21), a conserved RNA helicase of the DEAD-box family, serves as a key regulator of multiple fundamental cellular processes, including RNA metabolism, ribosome biogenesis, transcriptional regulation, and genomic stability. Our previous work has demonstrated an interaction between DDX21 and the nucleocapsid (N) protein of porcine deltacoronavirus (PDCoV). However, the specific role of DDX21 during PDCoV infection remains largely elusive. In the present study, we show that overexpression of DDX21 significantly restricts PDCoV infection in PK15, IPEC-J2, and HeLa cells, whereas knockout of DDX21 markedly enhances PDCoV replication in HeLa cells. Mechanistically, we identified that the N-terminal domainNTD of PDCoV N binds to the 1–217 amino acid region of DDX21, thereby inducing the cytoplasmic redistribution of DDX21 from the nucleus. Furthermore, DDX21-mediated suppression of PDCoV replication coincides with elevated interferon-β (IFN-β) production and interferon-stimulated geneISG expression. Importantly, PDCoV infection significantly downregulates DDX21 expression to antagonize its antiviral function, and similar antagonistic effects are observed for the coronaviruses from different genera. Collectively, our findings demonstrate that DDX21 interacts with the nucleocapsid protein and correlates with altered interferon signaling during coronavirus infection, which provides novel insights into the development of strategies for the prevention and control of coronavirus infections.
IMPORTANCE: Porcine deltacoronavirus (PDCoV) is an emerging swine coronavirus that infects pigs of all ages and causes substantial economic losses to the global swine industry. DEAD-box RNA helicase 21 (DDX21) acts as a key regulator of multiple fundamental cellular processes. However, its regulatory mechanism underlying PDCoV infection remains largely unclear. In this study, we found that DDX21 significantly inhibits PDCoV replication in vitro. Conversely, PDCoV infection markedly downregulates DDX21 expression. Furthermore, we demonstrated that the N-terminal 1–217 amino acid domain of DDX21 specifically interacts with the N-terminal domain (NTD) of the PDCoV nucleocapsid (N) protein. This interaction facilitates the nuclear-to-cytoplasmic translocation of DDX21, which correlates with an elevated host immune response. The upregulated interferon signature coincides with suppressed PDCoV replication. In addition, DDX21 exhibits antiviral activity against multiple coronaviruses from different genera. Collectively, this study provides novel insights into host-coronavirus interaction mechanisms and identifies a candidate target for anti-CoV therapeutic development.
Related
- SARS-CoV-2 Nucleocapsid Protein forms biomolecular condensates and interacts with ALS-associated RNA binding proteins in vitro
- Low-pH-induced conformational changes in the spike protein promote porcine deltacoronavirus infection by enhancing viral binding efficiency to the porcine aminopeptidase receptor
- Diagnostic accuracy of Mycobacterium tuberculosis antigen-induced interferon-γ-inducible protein 10 for latent tuberculosis infection among high-risk groups: a systematic review and meta-analysis
- The pathogenicity factor of DNA virus interacts with Arabidopsis deubiquitinases UBP12/13 to promote viral infection
- Interferon-λ signaling to maternal dendritic cells protects against congenital Zika virus infection
BibTeX
@article{zhang2026deadbox,
title = {{DEAD-box RNA helicase 21 interacts with the nucleocapsid protein and inhibits porcine deltacoronavirus infection through upregulation of interferon responses}},
author = {Nannan Zhang and Yanyan Xu and Yanying Chen and Mingyue Ma and Wenjie Lai and Shengwei Zhong and Gaofeng Cai and Ting Wang and Bin Li and Qi Peng and Hui Jiang},
journal = {Journal of Virology},
year = {2026},
month = sep,
doi = {10.1128/jvi.01169-26},
url = {https://doi.org/10.1128/jvi.01169-26},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - DEAD-box RNA helicase 21 interacts with the nucleocapsid protein and inhibits porcine deltacoronavirus infection through upregulation of interferon responses
AU - Nannan Zhang
AU - Yanyan Xu
AU - Yanying Chen
AU - Mingyue Ma
AU - Wenjie Lai
AU - Shengwei Zhong
AU - Gaofeng Cai
AU - Ting Wang
AU - Bin Li
AU - Qi Peng
AU - Hui Jiang
PY - 2026
DA - 2026/09/30
JO - Journal of Virology
DO - 10.1128/jvi.01169-26
UR - https://doi.org/10.1128/jvi.01169-26
AB - DEAD-box RNA helicase 21 (DDX21), a conserved RNA helicase of the DEAD-box family, serves as a key regulator of multiple fundamental cellular processes, including RNA metabolism, ribosome biogenesis, transcriptional regulation, and genomic stability. Our previous work has demonstrated an interaction between DDX21 and the nucleocapsid (N) protein of porcine deltacoronavirus (PDCoV). However, the specific role of DDX21 during PDCoV infection remains largely elusive. In the present study, we show that overexpression of DDX21 significantly restricts PDCoV infection in PK15, IPEC-J2, and HeLa cells, whereas knockout of DDX21 markedly enhances PDCoV replication in HeLa cells. Mechanistically, we identified that the N-terminal domainNTD of PDCoV N binds to the 1–217 amino acid region of DDX21, thereby inducing the cytoplasmic redistribution of DDX21 from the nucleus. Furthermore, DDX21-mediated suppression of PDCoV replication coincides with elevated interferon-β (IFN-β) production and interferon-stimulated geneISG expression. Importantly, PDCoV infection significantly downregulates DDX21 expression to antagonize its antiviral function, and similar antagonistic effects are observed for the coronaviruses from different genera. Collectively, our findings demonstrate that DDX21 interacts with the nucleocapsid protein and correlates with altered interferon signaling during coronavirus infection, which provides novel insights into the development of strategies for the prevention and control of coronavirus infections. IMPORTANCE: Porcine deltacoronavirus (PDCoV) is an emerging swine coronavirus that infects pigs of all ages and causes substantial economic losses to the global swine industry. DEAD-box RNA helicase 21 (DDX21) acts as a key regulator of multiple fundamental cellular processes. However, its regulatory mechanism underlying PDCoV infection remains largely unclear. In this study, we found that DDX21 significantly inhibits PDCoV replication in vitro. Conversely, PDCoV infection markedly downregulates DDX21 expression. Furthermore, we demonstrated that the N-terminal 1–217 amino acid domain of DDX21 specifically interacts with the N-terminal domain (NTD) of the PDCoV nucleocapsid (N) protein. This interaction facilitates the nuclear-to-cytoplasmic translocation of DDX21, which correlates with an elevated host immune response. The upregulated interferon signature coincides with suppressed PDCoV replication. In addition, DDX21 exhibits antiviral activity against multiple coronaviruses from different genera. Collectively, this study provides novel insights into host-coronavirus interaction mechanisms and identifies a candidate target for anti-CoV therapeutic development.
SN - 0022-538X
SN - 1098-5514
ER -