Genome-wide transcriptome analysis of porcine epidemic diarrhea virus virulent or avirulent strain-infected porcine small intestinal epithelial cells

Peng, Ouyang; Wang, Xiaona; Ashraf, Usama; Hu, Fangyu; Xia, Yongbo; Xu, Qiuping; Hu, Guangli; Xue, Chunyi; Cao, Yongchang; Zhang, Hao

doi:10.1016/j.virs.2022.01.011

Cited by 6 publications

(4 citation statements)

References 54 publications

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“…Restrained gene mRNA expression of ISGs may provide evidence of coronavirus immune evasion and provide guidance for the identification of therapy targets ( Figure 8 ). Our findings build upon our previous research, where we reported that the naturally generated virulent strain GDS01 evaded the immune system and promoted its proliferation by suppressing the TLR3/IFIT2 axis [ 37 ]. This underpins the concept of coronavirus immune evasion by imposing restrictions on immune-related gene expression.…”

Section: Discussionsupporting

confidence: 86%

Transcriptome Profiling of Vero E6 Cells during Original Parental or Cell-Attenuated Porcine Epidemic Diarrhea Virus Infection

Peng

et al. 2023

Viruses

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Porcine epidemic diarrhea virus (PEDV) has led to significant economic losses in the global porcine industry since the emergence of variant strains in 2010. The high mutability of coronaviruses endows PEDV with the ability to evade the host immune response, which impairs the effectiveness of vaccines. In our previous study, we generated a highly cell-passaged PEDV strain, CT-P120, which showed promise as a live attenuated vaccine candidate by providing satisfactory protection against variant PEDV infection in piglets. However, the mechanism by which the attenuated CT-P120 adapts to cells during passage, resulting in increased replication efficiency, remains unclear. To address this question, we conducted a comparative transcriptomic analysis of Vero E6 cells infected with either the original parental strain (CT-P10) or the cell-attenuated strain (CT-P120) of PEDV at 6, 12, and 24 h post-infection. Compared to CT-P10, CT-P120 infection resulted in a significant decrease in the number of differentially expressed genes (DEGs) at each time point. Functional enrichment analysis of genes revealed the activation of various innate immune-related pathways by CT-P10, notably attenuated during CT-P120 infection. To validate these results, we selected eight genes (TRAF3, IRF3, IFNL1, ISG15, NFKB1, MAP2K3, IL1A, and CCL2) involved in antiviral processes and confirmed their mRNA expression patterns using RT-qPCR, in line with the transcriptomic data. Subsequent protein-level analysis of selected genes via Western blotting and enzyme-linked immunosorbent assay corroborated these results, reinforcing the robustness of our findings. Collectively, our research elucidates the strategies underpinning PEDV attenuation and immune evasion, providing invaluable insights for the development of effective PEDV vaccines.

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Section: Discussionsupporting

confidence: 86%

Transcriptome Profiling of Vero E6 Cells during Original Parental or Cell-Attenuated Porcine Epidemic Diarrhea Virus Infection

Peng

et al. 2023

Viruses

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“…Besides, TGEV or PEDV infection reduced NHE3 activity and Na + uptake of IPEC-J2 cells, which may be associated with the imbalance of Na + in intestinal tissues, thus resulting in diarrhea in the infected animals (13). The differentially expressed genes (DEGs) in IPEC-J2 cells infected with virulent PEDV virus are mainly related to autophagy and apoptosis, while the DEGs were strongly enriched in immune responses/ inflammation in the avirulent PEDV group (14). TLR3 inhibited the replication of avirulent PEDV by increasing the IFIT2 expression (14).…”

Section: Introductionmentioning

confidence: 99%

“…The differentially expressed genes (DEGs) in IPEC-J2 cells infected with virulent PEDV virus are mainly related to autophagy and apoptosis, while the DEGs were strongly enriched in immune responses/ inflammation in the avirulent PEDV group (14). TLR3 inhibited the replication of avirulent PEDV by increasing the IFIT2 expression (14). Notably, a recent investigation showed that coinfection of TEGV and PEDV leads to recombinant chimeric swine enteric coronavirus (SeCoV) in Italy, Germany, and Slovakia (15)(16)(17)(18), which implies the urgency of prevention and control of virus-related diseases.…”

Section: Introductionmentioning

confidence: 99%

Differential Transcriptomics Analysis of IPEC-J2 Cells Single or Coinfected With Porcine Epidemic Diarrhea Virus and Transmissible Gastroenteritis Virus

et al. 2022

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Porcine epidemic diarrhea (PED) and transmissible gastroenteritis (TGE) caused by porcine epidemic diarrhea virus (PEDV) and transmissible gastroenteritis virus (TGEV) are two highly contagious intestinal diseases in the swine industry worldwide. Notably, coinfection of TGEV and PEDV is common in piglets with diarrhea-related diseases. In this study, intestinal porcine epithelial cells (IPEC-J2) were single or coinfected with PEDV and/or TGEV, followed by the comparison of differentially expressed genes (DEGs), especially interferon-stimulated genes (ISGs), between different groups via transcriptomics analysis and real-time qPCR. The antiviral activity of swine interferon-induced transmembrane protein 3 (sIFITM3) on PEDV and TGEV infection was also evaluated. The results showed that DEGs can be detected in the cells infected with PEDV, TGEV, and PEDV+TGEV at 12, 24, and 48 hpi, and the number of DEGs was the highest at 24 hpi. The DEGs are mainly annotated to the GO terms of protein binding, immune system process, organelle part, and intracellular organelle part. Furthermore, 90 ISGs were upregulated during PEDV or TGEV infection, 27 of which were associated with antiviral activity, including ISG15, OASL, IFITM1, and IFITM3. Furthermore, sIFITM3 can significantly inhibit PEDV and TGEV infection in porcine IPEC-J2 cells and/or monkey Vero cells. Besides, sIFITM3 can also inhibit vesicular stomatitis virus (VSV) replication in Vero cells. These results indicate that sIFITM3 has broad-spectrum antiviral activity.

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“…The autophagy pathway, positioned downstream of the PI3K/Akt/mTOR signaling cascade, represents a crucial metabolic process that safeguards cellular homeostasis [9]. Disruptions in autophagy mechanisms are intimately linked to the pathogenesis of various disorders, including tumors [10], neurodegenerative diseases [11], metabolic diseases [12], and immune disorders [13]. Among the autophagy signaling components, ULK (unc-51 like autophagy activating kinase) stands as the sole serine/threonine kinase-active protein [14].…”

Section: Introductionmentioning

confidence: 99%

Oxytocin Supplementation Demonstrates Potential in Reducing Breast Cancer Growth via Regulation of the PIK3CA/ULK1/Autophagy Axis

Xu,

Zhou,

Liu

et al. 2024

Preprint

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Breast cancer stands as a leading cause of morbidity and mortality among patients worldwide. The emerging trend in cancer prevention and treatment involves harnessing endogenous substances to regulate disease occurrence and progression. This study aimed to decipher the inhibitory effect of oxytocin on breast cancer and its underlying mechanism. Leveraging network pharmacology and molecular docking, we screened oxytocin's key targets in breast cancer. Our in vitro analysis revealed oxytocin's anti-proliferative, anti-migratory, and apoptosis-inducing properties in human breast cancer cell lines, MCF-7 and ZR-75-1. Additionally, oxytocin significantly suppressed the growth of MCF-7 transplanted tumors in nude mice. Western blot analysis detected oxytocin's modulation of PIK3CA expression and autophagy pathway factors, including ULK1, p62, LC3-Ⅰ, and LC3-Ⅱ, leading us to propose a mechanism involving the PIK3CA/ULK1/autophagy axis. The findings indicate that oxytocin effectively inhibits breast cancer cell proliferation and migration, promotes apoptosis, and reduces tumor growth, potentially through regulation of the PIK3CA/ULK1/autophagy pathway. Low-dose oxytocin supplementation emerges as a promising strategy for breast cancer prevention and treatment.

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Genome-wide transcriptome analysis of porcine epidemic diarrhea virus virulent or avirulent strain-infected porcine small intestinal epithelial cells

Cited by 6 publications

References 54 publications

Transcriptome Profiling of Vero E6 Cells during Original Parental or Cell-Attenuated Porcine Epidemic Diarrhea Virus Infection

Transcriptome Profiling of Vero E6 Cells during Original Parental or Cell-Attenuated Porcine Epidemic Diarrhea Virus Infection

Differential Transcriptomics Analysis of IPEC-J2 Cells Single or Coinfected With Porcine Epidemic Diarrhea Virus and Transmissible Gastroenteritis Virus

Oxytocin Supplementation Demonstrates Potential in Reducing Breast Cancer Growth via Regulation of the PIK3CA/ULK1/Autophagy Axis

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