HnRNPM inhibits pseudorabies virus replication by inducing apoptosis in infected cells
Xiaoxiao Zhao1, Yan Qiao1, Songjie Fan1
1College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, Henan 450046, China; Key Laboratory of Animal Biochemistry and Nutrition, Ministry of Agriculture and Rural Affairsof the People's Republic of China, Zhengzhou, Henan 450046, China; Key Laboratory of Animal Growth and Development, Zhengzhou, Henan 450046, China.
Abstract:
Heterogeneous nuclear ribonucleoproteins (hnRNPs) are a family of RNA-binding proteins that play crucial roles in RNA processing, transcriptional regulation, nucleocytoplasmic transport, and apoptosis. As a member of the hnRNP family, heterogeneous nuclear ribonucleoprotein M (hnRNPM) has been implicated in diverse cellular processes, including the regulation of tumor-associated gene expression, promotion of angiogenesis, enhancement of tumor cell invasion and metastasis, and modulation of RNA virus replication. However, the interaction between hnRNPM and pseudorabies virus (PRV) remains unexplored. In this study, we demonstrated that hnRNPM overexpression in PK15 and 3D4/21 cells significantly inhibited PRV replication, whereas hnRNPM knockdown enhanced viral replication. Although PRV infection did not alter total cellular hnRNPM levels, it induced the nuclear translocation of hnRNPM. Mechanistically, hnRNPM promoted apoptosis in PRV-infected cells by upregulating the expression of cleaved caspase-3, -6, and -7, as well as Bax, while downregulating Bcl-2. This apoptosis induction consequently suppressed PRV replication. Furthermore, hnRNPM was found to colocalize with caspase-6. Our findings reveal that hnRNPM inhibits PRV replication by inducing apoptosis in infected cells. These results not only enhance our understanding of PRV-host interactions but also highlight hnRNPM as a promising therapeutic target for the development of antiviral strategies against PRV.
Insights
Heterogeneous nuclear ribonucleoprotein M (hnRNPM) inhibits pseudorabies virus (PRV) replication by inducing apoptosis in infected cells. This finding reveals a novel antiviral mechanism and identifies hnRNPM as a potential therapeutic target.
Area of Science:
- Molecular Biology
- Virology
- Immunology
Background:
- Heterogeneous nuclear ribonucleoproteins (hnRNPs) are vital RNA-binding proteins involved in numerous cellular processes.
- hnRNPM, a specific hnRNP, influences gene expression, angiogenesis, and viral replication.
- The interaction between hnRNPM and pseudorabies virus (PRV) has not been previously investigated.
Purpose of the Study:
- To investigate the role of hnRNPM in PRV infection.
- To elucidate the mechanism by which hnRNPM affects PRV replication.
- To explore hnRNPM as a potential antiviral target against PRV.
Main Methods:
- Cell culture (PK15 and 3D4/21 cells) and PRV infection models.
- hnRNPM overexpression and knockdown experiments.
- Analysis of viral replication, apoptosis markers (caspase-3, -6, -7, Bax, Bcl-2), and protein localization (immunofluorescence).
Main Results:
- hnRNPM overexpression inhibited PRV replication; hnRNPM knockdown enhanced it.
- PRV infection induced nuclear translocation of hnRNPM without altering total levels.
- hnRNPM promoted apoptosis in infected cells, evidenced by increased cleaved caspases and Bax, and decreased Bcl-2, leading to suppressed viral replication. hnRNPM colocalized with caspase-6.
Conclusions:
- hnRNPM acts as a host antiviral factor against PRV by inducing apoptosis in infected cells.
- This study elucidates a novel PRV-host interaction mechanism.
- hnRNPM presents a potential therapeutic target for developing antiviral strategies against PRV.
