African Swine Fever Virus K205R Induces ER Stress and Consequently Activates Autophagy and the NF-κB Signaling Pathway

Autor: Qi Wang, Luyu Zhou, Jiang Wang, Dan Su, Dahua Li, Yongkun Du, Guoyu Yang, Gaiping Zhang, Beibei Chu
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Viruses, Vol 14, Iss 2, p 394 (2022)
Druh dokumentu: article
ISSN: 14020394
1999-4915
DOI: 10.3390/v14020394
Popis: African swine fever virus (ASFV) is responsible for enormous economic losses in the global swine industry. The ASFV genome encodes approximate 160 proteins, most of whose functions remain largely unknown. In this study, we examined the roles of ASFV K205R in endoplasmic reticulum (ER) stress, autophagy, and inflammation. We observed that K205R was located in both the cytosolic and membrane fractions, and formed stress granules in cells. Furthermore, K205R triggered ER stress and activated the unfolded protein response through activating the transcription factor 6, ER to nucleus signaling 1, and eukaryotic translation initiation factor 2 alpha kinase 3 (EIF2AK3/PERK) signaling pathways. Moreover, K205R inhibited the serine/threonine kinase 1 and the mechanistic target of the rapamycin kinase signaling pathway, thereby activating unc-51 like autophagy activating kinase 1, and hence autophagy. In addition, K205R stimulated the translocation of P65 into the nucleus and the subsequent activation of the nuclear factor kappa B (NF-κB) signaling pathway. Inhibition of ER stress with a PERK inhibitor attenuated K205R-induced autophagy and NF-κB activation. Our data demonstrated a previously uncharacterized role of ASFV K205R in ER stress, autophagy, and the NF-κB signaling pathway.
Databáze: Directory of Open Access Journals
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