Integrative Transcriptomics and Proteomics Analysis Provide a Deep Insight Into Bovine Viral Diarrhea Virus-Host Interactions During BVDV Infection

Ma, Yingying; Wang, Li; Jiang, Xiaoxia; Yao, Xin; Huang, Xinning; Zhou, Kun; Yang, Yaqi; Wang, Yixin; Sun, Xiaobo; Guan, Xiaohong; Xu, Yigang

doi:10.3389/fimmu.2022.862828

Cited by 12 publications

(9 citation statements)

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“…Many viral infections can activate the NF-κB signalling pathway, and then regulate the transcription and expression of the target genes involved in host innate immunity and inflammatory responses [ 24 , 25 ]. In our previous studies, to explore the underlying mechanisms of BVDV-host interactions, we performed an integrative analysis of transcriptomics and proteomics of the BVDV-infected bovine cells, and found that the significantly differentially expressed genes and proteins were mainly enriched in the NF-κB, NOD-like receptors (NLRs), TNF, Toll-like receptors, and apoptosis signaling pathways [ 26 , 27 ]. We also found that the NLR protein 3 (NLRP3) inflammasome components (NLRP3, ASC, and pro-caspase 1) were significantly upregulated in BVDV-infected bovine cells.…”

Section: Introductionmentioning

confidence: 99%

Identification of key proteins of cytopathic biotype bovine viral diarrhoea virus involved in activating NF-κB pathway in BVDV-induced inflammatory response

et al. 2022

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Bovine viral diarrhoea virus (BVDV) is the etiologic agent of bovine viral diarrhea-mucosal disease, one of the most important viral diseases in cattle, with inflammatory diarrhea, enteritis, and mucosa necrosis as the major clinical manifestations. NF-κB is an important transcription complex that regulates the expression of genes involved in inflammation and immune responses. NLRP3 inflammasome plays a key role in the development of inflammatory diseases. However, whether the activation of NF-κB is crucial for BVDV infection-induced inflammatory responses remains unclear. The results of our present study showed that BVDV infection significantly activated the NF-κB pathway and promoted the expression of NLRP3 inflammasome components (NLRP3, ASC, pro-caspase 1) as well inflammatory cytokine pro-IL-1β in BVDV-infected bovine cells, resulting in the cleavage of pro-caspase 1 and pro-IL-1β into active form caspase 1 and IL-1β. However, the levels of the NLRP3 inflammasome components and inflammatory cytokines were obviously inhibited, as well the cleavage of pro-caspase 1 and pro-IL-1β in the pre-treated bovine cells with NF-κB-specific inhibitors after BVDV infection. Further, cytopathic biotype BVDV (cpBVDV) Erns and NS5A proteins with their key functional domains contributed to BVDV-induced inflammatory responses via activating the NF-κB pathway were confirmed experimentally. Especially, the NS5A can promote cholesterol synthesis and accelerate its augmentation, further activating the NF-κB signalling pathway. Conclusively, our data elucidate that the activation of NF-κB signaling pathway plays a crucial role in cpBVDV infection-induced inflammatory responses.

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Section: Introductionmentioning

confidence: 99%

Identification of key proteins of cytopathic biotype bovine viral diarrhoea virus involved in activating NF-κB pathway in BVDV-induced inflammatory response

et al. 2022

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“…Our study observed a substantial increase in the expression of IFNLR1, a member of the IFN-λ receptor family. In contrast, a study on BVDV-infected MDBK cells demonstrated the downregulation of host antiviral protein expression in the early stages of infection [29]. The IL-17 family, recognized for its inflammatory cytokines, significantly contributes to innate and adaptive immunity.…”

Section: Discussionmentioning

confidence: 94%

“…Transcriptomics and proteomics techniques allow us to explore biological processes at the mRNA and protein levels, offering the potential for a systematic analysis of virus-host interactions. While studies have examined mRNA expression changes in different cell types upon the BVDV infection of cattle and goats [19,23,24], some scholars have delved into transcriptomic and proteomic data from BVDV-infected MDPK cells [29]. However, the majority of studies have focused on a single type of omics data, analyzing the changes in DEGs and DEPs following the BVDV infection of host cells.…”

Section: Discussionmentioning

confidence: 99%

Integrative Transcriptomics and Proteomics Analysis Reveals Immune Response Process in Bovine Viral Diarrhea Virus-1-Infected Peripheral Blood Mononuclear Cells

Zhang,

Wang

et al. 2023

Veterinary Sciences

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Bovine viral diarrhea virus (BVDV) causes bovine viral diarrhea-mucosal disease, inflicting substantial economic losses upon the global cattle industry. Peripheral blood mononuclear cells (PBMCs) are the central hub for immune responses during host-virus infection and have been recognized as crucial targets for BVDV infection. In order to elucidate the dynamics of host-BVDV-1 interaction, this study harnessed RNA-seq and iTRAQ methods to acquire an extensive dataset of transcriptomics and proteomics data from samples of BVDV-1-infected PBMCs at the 12-h post-infection mark. When compared to mock-infected PBMCs, we identified 344 differentially expressed genes (DEGs: a total of 234 genes with downregulated expression and 110 genes with upregulated expression) and 446 differentially expressed proteins (DEPs: a total of 224 proteins with downregulated expression and 222 proteins with upregulated expression). Selected DEGs and DEPs were validated through quantitative reverse transcriptase-polymerase chain reaction and parallel reaction monitoring. Gene ontology annotation and KEGG enrichment analysis underscored the significant enrichment of DEGs and DEPs in various immunity-related signaling pathways, including antigen processing and presentation, complement and coagulation cascades, cytokine-cytokine receptor interaction, and the NOD-like receptor signaling pathway, among others. Further analysis unveiled that those DEGs and DEPs with downregulated expression were predominantly associated with pathways such as complement and coagulation cascades, the interleukin-17 signaling pathway, cytokine-cytokine receptor interaction, the PI3K-Akt signaling pathway, the tumor necrosis factor signaling pathway, and the NOD-like receptor signaling pathway. Conversely, upregulated DEGs and DEPs were chiefly linked to metabolic pathways, oxidative phosphorylation, complement and coagulation cascades, and the RIG-I-like receptor signaling pathway. These altered genes and proteins shed light on the intense host-virus conflict within the immune realm. Our transcriptomics and proteomics data constitute a significant foundation for delving further into the interaction mechanism between BVDV and its host.

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“…To further study the relationship between BVDV and the host, the researchers found through transcriptomic and proteomic analysis of BVDV-infected MDBK cells.BVDV can inhibit host cell apoptosis and inhibit the expression of antiviral proteins and genes in the complement system, thereby promoting the proliferation of BVDV. At the same time, BVDV can also utilize host metabolic resources and cell autophagy to promote replication, which provides an important basis for further exploration of the mechanism of BVDV-host interaction, and also provides guidance for the eradication of BVD [ 94 – 96 ].…”

Section: Conclusion and Perspectivementioning

confidence: 99%

Non-structural proteins of bovine viral diarrhea virus

et al. 2022

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Bovine viral diarrhea virus (BVDV) belongs to the family Flaviviridae genus pestivirus. The viral genome is a single-stranded, positive-sense RNA that encodes four structural proteins (i.e., C, Erns, E1, and E2) and eight non-structural proteins (NSPs) (i.e., Npro, p7, NS2, NS3, NS4A, NS4B, NS5A, and NS5B). Cattle infected with BVDV exhibit a number of different clinical signs including diarrhea, abortion, and other reproductive disorders which have a serious impact on the cattle industry worldwide. Research on BVDV mainly focuses on its structural protein, however, progress in understanding the functions of the NSPs of BVDV has also been made in recent decades. The knowledge gained on the BVDV non-structural proteins is helpful to more fully understand the viral replication process and the molecular mechanism of viral persistent infection. This review focuses on the functions of BVDV NSPs and provides references for the identification of BVDV, the diagnosis and prevention of Bovine viral diarrhea mucosal disease (BVD-MD), and the development of vaccines.

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Integrative Transcriptomics and Proteomics Analysis Provide a Deep Insight Into Bovine Viral Diarrhea Virus-Host Interactions During BVDV Infection

Cited by 12 publications

References 84 publications

Identification of key proteins of cytopathic biotype bovine viral diarrhoea virus involved in activating NF-κB pathway in BVDV-induced inflammatory response

Identification of key proteins of cytopathic biotype bovine viral diarrhoea virus involved in activating NF-κB pathway in BVDV-induced inflammatory response

Integrative Transcriptomics and Proteomics Analysis Reveals Immune Response Process in Bovine Viral Diarrhea Virus-1-Infected Peripheral Blood Mononuclear Cells

Non-structural proteins of bovine viral diarrhea virus

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