Transcriptome analysis reveals that PRV XJ delgE/gI/TK protects against intestinal damage in nose-dropping-infected mice by regulating ECM-ITGA/ITGB-P-FAK

ABSTRACT Pseudorabies virus (PRV) is an ideal model for mechanistic investigations into α-herpesvirus. The neurotropism and latent infection of PRV have been extensively studied. Apart from neurological symptoms, diarrhea caused by PRV infection is also an essential cause of mortality in newborn and...

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Main Authors: Tong Xu, Yang Zhang, Qian Tao, Lei Xu, Si-Yuan Lai, Yan-Ru Ai, Jian-Bo Huang, Ben-Lu Yang, Ling Zhu, Zhi-Wen Xu
Format: Article
Language:English
Published: American Society for Microbiology 2025-01-01
Series:Microbiology Spectrum
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Online Access:https://journals.asm.org/doi/10.1128/spectrum.01828-24
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author Tong Xu
Yang Zhang
Qian Tao
Lei Xu
Si-Yuan Lai
Yan-Ru Ai
Jian-Bo Huang
Ben-Lu Yang
Ling Zhu
Zhi-Wen Xu
author_facet Tong Xu
Yang Zhang
Qian Tao
Lei Xu
Si-Yuan Lai
Yan-Ru Ai
Jian-Bo Huang
Ben-Lu Yang
Ling Zhu
Zhi-Wen Xu
author_sort Tong Xu
collection DOAJ
description ABSTRACT Pseudorabies virus (PRV) is an ideal model for mechanistic investigations into α-herpesvirus. The neurotropism and latent infection of PRV have been extensively studied. Apart from neurological symptoms, diarrhea caused by PRV infection is also an essential cause of mortality in newborn and weaned piglets. However, little research has been done on PRV invasion of the gut. To fill this gap, a nasal drip PRV-infection mouse model was developed, consisting of three groups: the challenged group (Group A), the immunization-challenged group (Group B), and a mock group (Group C). The results showed that immunization with PRV XJ delgE/gI/TK successfully prevented intestinal damage caused by PRV drop-nose infection. Subsequently, intestines were collected for transcriptional analysis. Differentially expressed genes analysis revealed that PRV XJ delgE/gI/TK was effective in reducing the organismal intestinal transcriptional activity caused by PRV. The Group A vs Group C and Group A vs Group B had similar Kyoto Encyclopedia of Genes and Genomes (KEGG)-enriched signaling pathways and the differentially expressed genes were primarily enriched in pathways, such as cell adhesion molecules, focal adhesion kinase, and actin cytoskeleton regulation. Notably, transcriptome analysis indicated that genes associated with the focal adhesion kinase (FAK) signaling pathway (ECM-ITGA/ITGB-p-FAK) were significantly more highly expressed in Group A than in Group B and Group C. The results of quantitative real-time PCR (RT-qPCR) and western blotting were consistent with KEGG analysis. Therefore, we hypothesized that PRV promotes self-infection through activation of the ECM-ITGA/ITGB-p-FAK signaling pathway and that PRV XJ delgE/gI/TK immunization could attenuate the intestinal damage caused by PRV by inhibiting the activation of this pathway.IMPORTANCEPseudorabies virus (PRV) poses a significant threat to the swine industry and public health due to its ability to infect multiple species, including humans, leading to substantial economic losses and potential health risks. This study addresses a critical gap in understanding the impact of PRV infection on the gut, which has been less explored compared to its neurological effects. By developing a drip-nose PRV-infection mouse model, the research indicated that PRV might promote self-infection through activation of the ECM-ITGA/ITGB-p-FAK signaling pathway, and PRV XJ delgE/gI/TK immunization effectively prevents intestinal damage by significantly reducing the expression of genes in the ECM-ITGA/ITGB-p-FAK signaling pathway. The research has important implications for the swine industry and public health by contributing to the development of better vaccines and treatments, ultimately helping to control PRV and prevent its cross-species transmission.
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spelling doaj-art-4416b5b3b9b74451ac9faa110248839f2025-01-07T14:05:18ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972025-01-0113110.1128/spectrum.01828-24Transcriptome analysis reveals that PRV XJ delgE/gI/TK protects against intestinal damage in nose-dropping-infected mice by regulating ECM-ITGA/ITGB-P-FAKTong Xu0Yang Zhang1Qian Tao2Lei Xu3Si-Yuan Lai4Yan-Ru Ai5Jian-Bo Huang6Ben-Lu Yang7Ling Zhu8Zhi-Wen Xu9College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, ChinaCollege of Veterinary Medicine, Sichuan Agricultural University, Chengdu, ChinaCollege of Veterinary Medicine, Sichuan Agricultural University, Chengdu, ChinaCollege of Veterinary Medicine, Sichuan Agricultural University, Chengdu, ChinaCollege of Veterinary Medicine, Sichuan Agricultural University, Chengdu, ChinaCollege of Veterinary Medicine, Sichuan Agricultural University, Chengdu, ChinaCollege of Veterinary Medicine, Sichuan Agricultural University, Chengdu, ChinaCollege Of Animal Science and Technology of Jiangxi Agricultural University, Nanchang, ChinaCollege of Veterinary Medicine, Sichuan Agricultural University, Chengdu, ChinaCollege of Veterinary Medicine, Sichuan Agricultural University, Chengdu, ChinaABSTRACT Pseudorabies virus (PRV) is an ideal model for mechanistic investigations into α-herpesvirus. The neurotropism and latent infection of PRV have been extensively studied. Apart from neurological symptoms, diarrhea caused by PRV infection is also an essential cause of mortality in newborn and weaned piglets. However, little research has been done on PRV invasion of the gut. To fill this gap, a nasal drip PRV-infection mouse model was developed, consisting of three groups: the challenged group (Group A), the immunization-challenged group (Group B), and a mock group (Group C). The results showed that immunization with PRV XJ delgE/gI/TK successfully prevented intestinal damage caused by PRV drop-nose infection. Subsequently, intestines were collected for transcriptional analysis. Differentially expressed genes analysis revealed that PRV XJ delgE/gI/TK was effective in reducing the organismal intestinal transcriptional activity caused by PRV. The Group A vs Group C and Group A vs Group B had similar Kyoto Encyclopedia of Genes and Genomes (KEGG)-enriched signaling pathways and the differentially expressed genes were primarily enriched in pathways, such as cell adhesion molecules, focal adhesion kinase, and actin cytoskeleton regulation. Notably, transcriptome analysis indicated that genes associated with the focal adhesion kinase (FAK) signaling pathway (ECM-ITGA/ITGB-p-FAK) were significantly more highly expressed in Group A than in Group B and Group C. The results of quantitative real-time PCR (RT-qPCR) and western blotting were consistent with KEGG analysis. Therefore, we hypothesized that PRV promotes self-infection through activation of the ECM-ITGA/ITGB-p-FAK signaling pathway and that PRV XJ delgE/gI/TK immunization could attenuate the intestinal damage caused by PRV by inhibiting the activation of this pathway.IMPORTANCEPseudorabies virus (PRV) poses a significant threat to the swine industry and public health due to its ability to infect multiple species, including humans, leading to substantial economic losses and potential health risks. This study addresses a critical gap in understanding the impact of PRV infection on the gut, which has been less explored compared to its neurological effects. By developing a drip-nose PRV-infection mouse model, the research indicated that PRV might promote self-infection through activation of the ECM-ITGA/ITGB-p-FAK signaling pathway, and PRV XJ delgE/gI/TK immunization effectively prevents intestinal damage by significantly reducing the expression of genes in the ECM-ITGA/ITGB-p-FAK signaling pathway. The research has important implications for the swine industry and public health by contributing to the development of better vaccines and treatments, ultimately helping to control PRV and prevent its cross-species transmission.https://journals.asm.org/doi/10.1128/spectrum.01828-24pseudorabies virusfocal adhesion kinasetranscriptomedrip-nose PRV-infection
spellingShingle Tong Xu
Yang Zhang
Qian Tao
Lei Xu
Si-Yuan Lai
Yan-Ru Ai
Jian-Bo Huang
Ben-Lu Yang
Ling Zhu
Zhi-Wen Xu
Transcriptome analysis reveals that PRV XJ delgE/gI/TK protects against intestinal damage in nose-dropping-infected mice by regulating ECM-ITGA/ITGB-P-FAK
Microbiology Spectrum
pseudorabies virus
focal adhesion kinase
transcriptome
drip-nose PRV-infection
title Transcriptome analysis reveals that PRV XJ delgE/gI/TK protects against intestinal damage in nose-dropping-infected mice by regulating ECM-ITGA/ITGB-P-FAK
title_full Transcriptome analysis reveals that PRV XJ delgE/gI/TK protects against intestinal damage in nose-dropping-infected mice by regulating ECM-ITGA/ITGB-P-FAK
title_fullStr Transcriptome analysis reveals that PRV XJ delgE/gI/TK protects against intestinal damage in nose-dropping-infected mice by regulating ECM-ITGA/ITGB-P-FAK
title_full_unstemmed Transcriptome analysis reveals that PRV XJ delgE/gI/TK protects against intestinal damage in nose-dropping-infected mice by regulating ECM-ITGA/ITGB-P-FAK
title_short Transcriptome analysis reveals that PRV XJ delgE/gI/TK protects against intestinal damage in nose-dropping-infected mice by regulating ECM-ITGA/ITGB-P-FAK
title_sort transcriptome analysis reveals that prv xj delge gi tk protects against intestinal damage in nose dropping infected mice by regulating ecm itga itgb p fak
topic pseudorabies virus
focal adhesion kinase
transcriptome
drip-nose PRV-infection
url https://journals.asm.org/doi/10.1128/spectrum.01828-24
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