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Highly Pathogenic PRRSV-Infected Alveolar Macrophages Impair the Function of Pulmonary Microvascular Endothelial Cells

The porcine reproductive and respiratory syndrome virus (PRRSV), especially the highly pathogenic strains, can cause serious acute lung injury (ALI), characterized by extensive hemorrhage, inflammatory cells and serous fluid infiltration in the lung vascular system. Meanwhile, the pulmonary microvas...

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Autores principales: Sun, Weifeng, Wu, Weixin, Jiang, Nan, Ge, Xinna, Zhang, Yongning, Han, Jun, Guo, Xin, Zhou, Lei, Yang, Hanchun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8948932/
https://www.ncbi.nlm.nih.gov/pubmed/35336858
http://dx.doi.org/10.3390/v14030452
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author Sun, Weifeng
Wu, Weixin
Jiang, Nan
Ge, Xinna
Zhang, Yongning
Han, Jun
Guo, Xin
Zhou, Lei
Yang, Hanchun
author_facet Sun, Weifeng
Wu, Weixin
Jiang, Nan
Ge, Xinna
Zhang, Yongning
Han, Jun
Guo, Xin
Zhou, Lei
Yang, Hanchun
author_sort Sun, Weifeng
collection PubMed
description The porcine reproductive and respiratory syndrome virus (PRRSV), especially the highly pathogenic strains, can cause serious acute lung injury (ALI), characterized by extensive hemorrhage, inflammatory cells and serous fluid infiltration in the lung vascular system. Meanwhile, the pulmonary microvascular endothelial cells (PMVECs) are essential for forming the air–blood barrier and keeping the water–salt balance to prevent leakage of circulating nutrients, solutes, and fluid into the underlying tissues. As well, they tightly regulate the influx of immune cells. To determine the possible relationship between the PMVECs’ function changes and lung vascular permeability during PRRSV infection, the PMVECs were co-cultured with HP-PRRSV-inoculated primary pulmonary alveolar macrophages (PAMs) in transwell model, and then the RNA sequencing (RNA-seq) and comprehensive bioinformatics analysis were carried out to characterize the dynamic transcriptome landscapes of PMVECs. In total, 16,489 annotated genes were identified, with 275 upregulated and 270 downregulated differentially expressed genes (DEGs) were characterized at both 18 and 24 h post PRRSV inoculation. The GO terms and KEGG pathways analysis indicated that the immune response, metabolic pathways, cell death, cytokine–cytokine receptor interaction, viral responses, and apoptotic process are significantly regulated upon co-culture with PRRSV-infected PAMs. Moreover, according to the TERR and dextran flux assay results, dysregulation of TJ proteins, including CLDN1, CLDN4, CLDN8, and OCLN, is further confirmed to correlate with the increased permeability of PMVECs. These transcriptome profiles and DEGs will provide valuable clues for further exploring the roles of PMVECs in PRRSV-induced ALI in the future.
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spelling pubmed-89489322022-03-26 Highly Pathogenic PRRSV-Infected Alveolar Macrophages Impair the Function of Pulmonary Microvascular Endothelial Cells Sun, Weifeng Wu, Weixin Jiang, Nan Ge, Xinna Zhang, Yongning Han, Jun Guo, Xin Zhou, Lei Yang, Hanchun Viruses Article The porcine reproductive and respiratory syndrome virus (PRRSV), especially the highly pathogenic strains, can cause serious acute lung injury (ALI), characterized by extensive hemorrhage, inflammatory cells and serous fluid infiltration in the lung vascular system. Meanwhile, the pulmonary microvascular endothelial cells (PMVECs) are essential for forming the air–blood barrier and keeping the water–salt balance to prevent leakage of circulating nutrients, solutes, and fluid into the underlying tissues. As well, they tightly regulate the influx of immune cells. To determine the possible relationship between the PMVECs’ function changes and lung vascular permeability during PRRSV infection, the PMVECs were co-cultured with HP-PRRSV-inoculated primary pulmonary alveolar macrophages (PAMs) in transwell model, and then the RNA sequencing (RNA-seq) and comprehensive bioinformatics analysis were carried out to characterize the dynamic transcriptome landscapes of PMVECs. In total, 16,489 annotated genes were identified, with 275 upregulated and 270 downregulated differentially expressed genes (DEGs) were characterized at both 18 and 24 h post PRRSV inoculation. The GO terms and KEGG pathways analysis indicated that the immune response, metabolic pathways, cell death, cytokine–cytokine receptor interaction, viral responses, and apoptotic process are significantly regulated upon co-culture with PRRSV-infected PAMs. Moreover, according to the TERR and dextran flux assay results, dysregulation of TJ proteins, including CLDN1, CLDN4, CLDN8, and OCLN, is further confirmed to correlate with the increased permeability of PMVECs. These transcriptome profiles and DEGs will provide valuable clues for further exploring the roles of PMVECs in PRRSV-induced ALI in the future. MDPI 2022-02-22 /pmc/articles/PMC8948932/ /pubmed/35336858 http://dx.doi.org/10.3390/v14030452 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sun, Weifeng
Wu, Weixin
Jiang, Nan
Ge, Xinna
Zhang, Yongning
Han, Jun
Guo, Xin
Zhou, Lei
Yang, Hanchun
Highly Pathogenic PRRSV-Infected Alveolar Macrophages Impair the Function of Pulmonary Microvascular Endothelial Cells
title Highly Pathogenic PRRSV-Infected Alveolar Macrophages Impair the Function of Pulmonary Microvascular Endothelial Cells
title_full Highly Pathogenic PRRSV-Infected Alveolar Macrophages Impair the Function of Pulmonary Microvascular Endothelial Cells
title_fullStr Highly Pathogenic PRRSV-Infected Alveolar Macrophages Impair the Function of Pulmonary Microvascular Endothelial Cells
title_full_unstemmed Highly Pathogenic PRRSV-Infected Alveolar Macrophages Impair the Function of Pulmonary Microvascular Endothelial Cells
title_short Highly Pathogenic PRRSV-Infected Alveolar Macrophages Impair the Function of Pulmonary Microvascular Endothelial Cells
title_sort highly pathogenic prrsv-infected alveolar macrophages impair the function of pulmonary microvascular endothelial cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8948932/
https://www.ncbi.nlm.nih.gov/pubmed/35336858
http://dx.doi.org/10.3390/v14030452
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