PMID- 35336858 OWN - NLM STAT- MEDLINE DCOM- 20220414 LR - 20220414 IS - 1999-4915 (Electronic) IS - 1999-4915 (Linking) VI - 14 IP - 3 DP - 2022 Feb 22 TI - Highly Pathogenic PRRSV-Infected Alveolar Macrophages Impair the Function of Pulmonary Microvascular Endothelial Cells. LID - 10.3390/v14030452 [doi] LID - 452 AB - 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. FAU - Sun, Weifeng AU - Sun W AD - Key Laboratory of Animal Epidemiology of Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China. FAU - Wu, Weixin AU - Wu W AUID- ORCID: 0000-0002-0734-3247 AD - Key Laboratory of Animal Epidemiology of Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China. FAU - Jiang, Nan AU - Jiang N AD - Key Laboratory of Animal Epidemiology of Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China. FAU - Ge, Xinna AU - Ge X AUID- ORCID: 0000-0002-5368-9687 AD - Key Laboratory of Animal Epidemiology of Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China. FAU - Zhang, Yongning AU - Zhang Y AD - Key Laboratory of Animal Epidemiology of Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China. FAU - Han, Jun AU - Han J AUID- ORCID: 0000-0002-7104-7223 AD - Key Laboratory of Animal Epidemiology of Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China. FAU - Guo, Xin AU - Guo X AD - Key Laboratory of Animal Epidemiology of Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China. FAU - Zhou, Lei AU - Zhou L AUID- ORCID: 0000-0002-8837-3965 AD - Key Laboratory of Animal Epidemiology of Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China. FAU - Yang, Hanchun AU - Yang H AUID- ORCID: 0000-0003-3359-3925 AD - Key Laboratory of Animal Epidemiology of Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220222 PL - Switzerland TA - Viruses JT - Viruses JID - 101509722 SB - IM MH - Animals MH - Endothelial Cells MH - Lung/pathology MH - Macrophages, Alveolar MH - *Porcine Reproductive and Respiratory Syndrome/metabolism MH - *Porcine respiratory and reproductive syndrome virus MH - Swine PMC - PMC8948932 OTO - NOTNLM OT - cytokines OT - porcine reproductive and respiratory syndrome virus (PRRSV) OT - pulmonary microvascular endothelial cells (PMVECs) OT - tight junctions (TJs) OT - transcriptome analysis OT - transwell co-cultures COIS- The authors declare no conflict of interest. EDAT- 2022/03/27 06:00 MHDA- 2022/04/15 06:00 PMCR- 2022/02/22 CRDT- 2022/03/26 01:07 PHST- 2022/01/28 00:00 [received] PHST- 2022/02/16 00:00 [revised] PHST- 2022/02/17 00:00 [accepted] PHST- 2022/03/26 01:07 [entrez] PHST- 2022/03/27 06:00 [pubmed] PHST- 2022/04/15 06:00 [medline] PHST- 2022/02/22 00:00 [pmc-release] AID - v14030452 [pii] AID - viruses-14-00452 [pii] AID - 10.3390/v14030452 [doi] PST - epublish SO - Viruses. 2022 Feb 22;14(3):452. doi: 10.3390/v14030452.