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A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF3
Published on: January 24, 2016
HnRNPK promotes SVCV replication by stabilizing viral phosphoprotein and targeting IRF3 to suppress type I interferon
Yanwei Zhang1, Xin Lin1, Mingyi Li1
1College of Fisheries, Xinyang Agriculture and Forestry University, Xinyang, 464000, China.
Abstract:
Heterogeneous nuclear ribonucleoprotein K (hnRNPK) is a multifunctional RNA-binding protein implicated in various cellular processes, yet its role in fish antiviral immunity and viral replication remains poorly understood. In this study, we found that common carp (Cyprinus carpio) hnRNPK expression was markedly upregulated following SVCV infection or poly(I:C) stimulation, accompanied by its translocation from the nucleus to the cytoplasm. Overexpression of hnRNPK enhanced viral replication, as reflected by increased viral gene expression and viral titers. Mechanistically, hnRNPK interacted with the SVCV phosphoprotein (P) and promoted its stability. Additionally, hnRNPK suppressed type I interferon (IFN) production by interacting with key components of the RLR signaling pathway, including MITA, TBK1, IRF3, and IRF7. Notably, hnRNPK facilitated IRF3 degradation and impeded its nuclear translocation, thereby negatively regulating the type I IFN response. Collectively, these findings indicate that hnRNPK promotes SVCV replication through a dual mechanism: stabilizing the viral P protein and attenuating the host type I interferon response by targeting IRF3. This study provides new insights into the immune evasion strategies employed by SVCV and highlights hnRNPK as a potential target for antiviral intervention in lower vertebrates.
Insights
Heterogeneous nuclear ribonucleoprotein K (hnRNPK) promotes viral replication in fish by stabilizing viral proteins and suppressing the host interferon response. This protein offers a potential target for antiviral strategies in aquatic animals.
Area of Science:
- Immunology
- Virology
- Molecular Biology
Background:
- Heterogeneous nuclear ribonucleoprotein K (hnRNPK) is a key RNA-binding protein involved in cellular processes.
- Its specific role in fish antiviral immunity and viral replication is not well understood.
Purpose of the Study:
- To investigate the function of hnRNPK in common carp antiviral immunity against SVCV.
- To elucidate the molecular mechanisms by which hnRNPK influences viral replication and host immune responses.
Main Methods:
- Analyzing hnRNPK expression levels in SVCV-infected carp.
- Investigating hnRNPK's interaction with viral proteins and host immune factors.
- Assessing the impact of hnRNPK overexpression on viral replication and interferon production.
Main Results:
- hnRNPK expression increased upon SVCV infection and translocated to the cytoplasm.
- hnRNPK overexpression enhanced viral replication by stabilizing the SVCV phosphoprotein (P).
- hnRNPK suppressed type I interferon production by targeting IRF3, inhibiting its nuclear translocation and promoting degradation.
Conclusions:
- hnRNPK promotes SVCV replication via dual mechanisms: stabilizing the viral P protein and suppressing the type I interferon response through IRF3.
- hnRNPK plays a significant role in SVCV immune evasion strategies.
- hnRNPK represents a potential therapeutic target for antiviral interventions in fish.
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