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Porcine circovirus type 2 ORF5 protein induces endoplasmic reticulum stress and unfolded protein response in porcine alveolar macrophages
- Ouyang, Yueling, Xu, Lei, Lv, Jiangman, Hou, Yufeng, Fan, Zhixin, Xu, Panpan, Jiang, Yanfen, Wu, Mengmeng, Li, Ran, Zhang, Yanming, Guo, Kangkang
- Archives of virology 2019 v.164 no.5 pp. 1323-1334
- Porcine circovirus, Porcine circovirus-2, Western blotting, apoptosis, coat proteins, endoplasmic reticulum, endoplasmic reticulum stress, enzymes, industry, inositols, macrophages, open reading frames, pathogenesis, pathogens, quantitative polymerase chain reaction, signal transduction, swine, transcription factors, transmission electron microscopy, unfolded protein response, viral nonstructural proteins, viruses
- Porcine circovirus type 2 (PCV2) is the essential infectious agent causing porcine circovirus-associated disease (PCVD) in pigs and one of the important viruses that severely jeopardize the swine husbandry industry. PCV2 elicits the unfolded protein response (UPR) via activation of the PERK pathway, and its capsid protein (Cap) has also been found to induce UPR with subsequent activation of apoptosis. The open reading frame 5 (ORF5) protein is a recently discovered non-structural protein, and its function in PCV2 pathogenesis remains unknown. The aim of this study was to determine whether the PCV2 ORF5 protein could induce endoplasmic reticulum stress (ERS) and UPR in porcine alveolar macrophages (PAMs). pEGFP-tagged ORF5 protein was transiently overexpressed in PAMs. Transmission electron microscopy (TEM) was employed to examine changes in ER morphology, and quantitative real-time PCR and western blotting analysis were used to measure UPR-related cell signaling alterations. We found that the ORF5 protein triggers swelling and degranulation of the ER and upregulates the expression of ERS markers. Further experiments demonstrated that the PCV2 ORF5 protein induces ERS and UPR via the PERK (RNA-activated protein kinase-like endoplasmic reticulum kinase), ATF6 (activating transcription factor 6) and IRE1 (inositol requiring enzyme 1) signaling pathways. Together with previous studies, we provide new information on the ERS-UPR induced by the PCV2 ORF5 protein.