Phosphorylation of VP1 Mediated by CDK1-Cyclin B1 Facilitates Infectious Bursal Disease Virus Replication

Hu, Xifeng; Chen, Zheng; Wu, Xiangdong; Ding, Zhen; Huang, Yu; Fu, Qiuling; Chen, Zhen; Wu, Huansheng

doi:10.1128/jvi.01941-22

Cited by 6 publications

(4 citation statements)

References 70 publications

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“…Besides the down regulation of CDK1, our findings indicate a significant down-regulation of genes associated with the protein synthesis system as evidenced by extensive down-regulated genes enriched in the ribosome-related pathway, RNA transport, spliceosome, ribosome biosynthesis in eukaryotes. Recently, Wu and Hur (60) confirmed that the CDK1-cyclin B1 complex phosphorylates VP1, thereby facilitating IBDV replication. Collectively, these results suggest that NN1172 may arrest cell cycle at G2/M stage, which may enhance virus replication, thymus damage and disease progresses.…”

Section: Discussionmentioning

confidence: 98%

RNA-seq reveals role of cell-cycle regulating genes in the pathogenicity of a field very virulent infectious bursal disease virus

Chen,

Wang,

et al. 2024

Front. Vet. Sci.

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Infectious bursal disease virus (IBDV) infection causes highly contagious and immunosuppressive disease in poultry. The thymus, serving as the primary organ for T cell maturation and differentiation, plays an important role in the pathogenicity of IBDV in the infected chickens. However, there are no reports on the molecular pathogenesis of IBDV in the thymus currently. The aim of the study was to elucidate the molecular mechanisms underlying the pathogenicity of a field very virulent (vv) IBDV strain NN1172 in the thymus of SPF chickens using integrative transcriptomic and proteomic analyses. Our results showed that a total of 4,972 Differentially expressed genes (DEGs) in the thymus of NN1172-infected chickens by transcriptomic analysis, with 2,796 up-regulated and 2,176 down-regulated. Meanwhile, the proteomic analysis identified 726 differentially expressed proteins (DEPs) in the infected thymus, with 289 up-regulated and 437 down-regulated. Overall, a total of 359 genes exhibited differentially expression at both mRNA and protein levels, with 134 consistently up-regulated and 198 genes consistently down-regulated, as confirmed through a comparison of the RNA-seq and the proteomic datasets. The gene ontology (GO) analysis unveiled the involvement of both DEGs and DEPs in diverse categories encompassing cellular components, biological processes, and molecular functions in the pathological changes in IBDV-infected thymus. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the host mainly displayed severely disruption of cell survival/repair, proliferation and metabolism pathway, meanwhile, the infection triggers antiviral immune activation with a potential emphasis on the MDA5 pathway. Network inference analysis identified seven core hub genes, which include CDK1, TYMS, MCM5, KIF11, CCNB2, MAD2L1, and MCM4. These genes are all associated with cell-cycle regulating pathway and are likely key mediators in the pathogenesis induced by NN1172 infection in the thymus. This study discovered dominant pathways and genes which enhanced our understanding of the molecular mechanisms underlying IBDV pathogenesis in the thymus.

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Section: Discussionmentioning

confidence: 98%

RNA-seq reveals role of cell-cycle regulating genes in the pathogenicity of a field very virulent infectious bursal disease virus

Chen,

Wang,

et al. 2024

Front. Vet. Sci.

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“…Infectious bursal disease virus (IBDV), a segmented dsRNA virus belonging to the Birnaviridae family, infects B lymphocytes in the bursa of Fabricius and causes a highly contagious, acute, and immunosuppressive infectious bursal disease in young chickens. The RNA-dependent RNA polymerase protein VP1 is involved in viral genome replication, transcription, and packaging, and its catalytic activity can be regulated by PTMs, such as sumoylation and phosphorylation 144 , 145 . Arginine methylation by PRMT also affects VP1 activity and viral infection (Figure 7 A).…”

Section: Prmts Regulate Viral Infectionmentioning

confidence: 99%

Protein arginine methylation in viral infection and antiviral immunity

Zheng,

Chen,

Ren

et al. 2023

Int. J. Biol. Sci.

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Protein arginine methyltransferase (PRMT)-mediated arginine methylation is an important post-transcriptional modification that regulates various cellular processes including epigenetic gene regulation, genome stability maintenance, RNA metabolism, and stress-responsive signal transduction. The varying substrates and biological functions of arginine methylation in cancer and neurological diseases have been extensively discussed, providing a rationale for targeting PRMTs in clinical applications. An increasing number of studies have demonstrated an interplay between arginine methylation and viral infections. PRMTs have been found to methylate and regulate several host cell proteins and different functional types of viral proteins, such as viral capsids, mRNA exporters, transcription factors, and latency regulators. This modulation affects their activity, subcellular localization, protein-nucleic acid and protein-protein interactions, ultimately impacting their roles in various virus-associated processes. In this review, we discuss the classification, structure, and regulation of PRMTs and their pleiotropic biological functions through the methylation of histones and non-histones. Additionally, we summarize the broad spectrum of PRMT substrates and explore their intricate effects on various viral infection processes and antiviral innate immunity. Thus, comprehending the regulation of arginine methylation provides a critical foundation for understanding the pathogenesis of viral diseases and uncovering opportunities for antiviral therapy.

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“…For instance, in the case of SARS-CoV-2, nsp12 was shown to recruit CDK2 through its NiRAN domain (13). The polymerase of infectious bursal disease virus (IBDV) can interact with the CDK1-cyclinB1 complex (11). Polymerases of several flaviviruses including West Nile virus, Usutu virus, Zika virus and HCV were all shown to interact with AKT/PKB and to be phosphorylated by these kinases in vitro (19, 34).…”

Section: Recruitment Of Host Kinases By Protein-protein Interactionmentioning

confidence: 99%

Regulation of viral RNA-dependent RNA polymerases by phosphorylation

Duflos

Michiels

2023

Front. Virol.

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RNA viruses encode an RNA-dependent RNA polymerase (RdRp), which is essential for transcription and replication of their genome since host cells lack equivalent enzymes. RdRp residues were shown to be phosphorylated by host kinases in several human, animal or plant viruses including flaviviruses, picornaviruses, coronaviruses, influenza viruses and tymoviruses. RdRps can be phosphorylated on several residues by distinct host kinases. Phosphomimetic mutations of identified phosphorylated residues either positively or negatively regulate RNA synthesis or association of RdRps with RNA or other proteins. Interestingly, some RdRps evolved to recruit cellular kinases through direct protein-protein interaction, likely to promote or to tightly control their own phosphorylation. Given the essential nature of RdRps for RNA virus replication, a better knowledge of RdRps’ phosphorylation is expected to facilitate the design of future drugs that strongly affect polymerase activity.

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Phosphorylation of VP1 Mediated by CDK1-Cyclin B1 Facilitates Infectious Bursal Disease Virus Replication

Abstract: Infectious bursal disease virus still poses a great economic threat to the global poultry farming industry. Detailed information on the steps of viral genome replication is essential for the development of antiviral therapeutics.

Cited by 6 publications

References 70 publications

RNA-seq reveals role of cell-cycle regulating genes in the pathogenicity of a field very virulent infectious bursal disease virus

RNA-seq reveals role of cell-cycle regulating genes in the pathogenicity of a field very virulent infectious bursal disease virus

Protein arginine methylation in viral infection and antiviral immunity

Regulation of viral RNA-dependent RNA polymerases by phosphorylation

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