TRAF6 is a novel NS3-interacting protein that inhibits classical swine fever virus replication

Abstract Classical swine fever virus (CSFV) non-structural protein 3 (NS3) is a multifunctional non-structural protein that plays a major role in viral replication. However, how exactly NS3 exerts these functions remains unknown. Here, we identified tumour necrosis factor receptor-associated factor...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Huifang Lv, Wang Dong, Zhi Cao, Xiaomeng Li, Jie Wang, Gui Qian, Qizhuang Lv, Chengbao Wang, Kangkang Guo, Yanming Zhang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6a8010dd76aa41b084caec2c1ca317c4
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:6a8010dd76aa41b084caec2c1ca317c4
record_format	dspace
spelling	oai:doaj.org-article:6a8010dd76aa41b084caec2c1ca317c42021-12-02T16:06:03ZTRAF6 is a novel NS3-interacting protein that inhibits classical swine fever virus replication10.1038/s41598-017-06934-12045-2322https://doaj.org/article/6a8010dd76aa41b084caec2c1ca317c42017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06934-1https://doaj.org/toc/2045-2322Abstract Classical swine fever virus (CSFV) non-structural protein 3 (NS3) is a multifunctional non-structural protein that plays a major role in viral replication. However, how exactly NS3 exerts these functions remains unknown. Here, we identified tumour necrosis factor receptor-associated factor 6 (TRAF6) as a novel NS3-interacting protein via yeast two-hybrid analysis, co-immunoprecipitation, and glutathione S-transferase pull-down assays. Furthermore, we observed that TRAF6 overexpression significantly inhibited CSFV replication, and TRAF6 knockdown promoted CSFV replication in porcine alveolar macrophages. Additionally, TRAF6 was degraded during CSFV infection or NS3 expression exclusively, indicating that CSFV and TRAF6 were mutually antagonistic and that TRAF6 degradation might contribute to persistent CSFV replication. Moreover, nuclear factor-kappa B (NF-κB) activity and interferon (IFN)-β and interleukin (IL)-6 expression were increased in TRAF6-overexpressing cells, whereas TRAF6-knockdown cells exhibited decreased NF-κB activity and IFN-β and IL-6 levels. Notably, TRAF6 overexpression did not reduce CSFV replication following inhibition of NF-κB activation by p65 knockdown. Our findings revealed that TRAF6 inhibits CSFV replication via activation of NF-κB-signalling pathways along with increases in the expression of its targets IFN-β and IL-6. This work addresses a novel aspect concerning the regulation of innate antiviral immune response during CSFV infection.Huifang LvWang DongZhi CaoXiaomeng LiJie WangGui QianQizhuang LvChengbao WangKangkang GuoYanming ZhangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Huifang Lv Wang Dong Zhi Cao Xiaomeng Li Jie Wang Gui Qian Qizhuang Lv Chengbao Wang Kangkang Guo Yanming Zhang TRAF6 is a novel NS3-interacting protein that inhibits classical swine fever virus replication
description	Abstract Classical swine fever virus (CSFV) non-structural protein 3 (NS3) is a multifunctional non-structural protein that plays a major role in viral replication. However, how exactly NS3 exerts these functions remains unknown. Here, we identified tumour necrosis factor receptor-associated factor 6 (TRAF6) as a novel NS3-interacting protein via yeast two-hybrid analysis, co-immunoprecipitation, and glutathione S-transferase pull-down assays. Furthermore, we observed that TRAF6 overexpression significantly inhibited CSFV replication, and TRAF6 knockdown promoted CSFV replication in porcine alveolar macrophages. Additionally, TRAF6 was degraded during CSFV infection or NS3 expression exclusively, indicating that CSFV and TRAF6 were mutually antagonistic and that TRAF6 degradation might contribute to persistent CSFV replication. Moreover, nuclear factor-kappa B (NF-κB) activity and interferon (IFN)-β and interleukin (IL)-6 expression were increased in TRAF6-overexpressing cells, whereas TRAF6-knockdown cells exhibited decreased NF-κB activity and IFN-β and IL-6 levels. Notably, TRAF6 overexpression did not reduce CSFV replication following inhibition of NF-κB activation by p65 knockdown. Our findings revealed that TRAF6 inhibits CSFV replication via activation of NF-κB-signalling pathways along with increases in the expression of its targets IFN-β and IL-6. This work addresses a novel aspect concerning the regulation of innate antiviral immune response during CSFV infection.
format	article
author	Huifang Lv Wang Dong Zhi Cao Xiaomeng Li Jie Wang Gui Qian Qizhuang Lv Chengbao Wang Kangkang Guo Yanming Zhang
author_facet	Huifang Lv Wang Dong Zhi Cao Xiaomeng Li Jie Wang Gui Qian Qizhuang Lv Chengbao Wang Kangkang Guo Yanming Zhang
author_sort	Huifang Lv
title	TRAF6 is a novel NS3-interacting protein that inhibits classical swine fever virus replication
title_short	TRAF6 is a novel NS3-interacting protein that inhibits classical swine fever virus replication
title_full	TRAF6 is a novel NS3-interacting protein that inhibits classical swine fever virus replication
title_fullStr	TRAF6 is a novel NS3-interacting protein that inhibits classical swine fever virus replication
title_full_unstemmed	TRAF6 is a novel NS3-interacting protein that inhibits classical swine fever virus replication
title_sort	traf6 is a novel ns3-interacting protein that inhibits classical swine fever virus replication
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/6a8010dd76aa41b084caec2c1ca317c4
work_keys_str_mv	AT huifanglv traf6isanovelns3interactingproteinthatinhibitsclassicalswinefevervirusreplication AT wangdong traf6isanovelns3interactingproteinthatinhibitsclassicalswinefevervirusreplication AT zhicao traf6isanovelns3interactingproteinthatinhibitsclassicalswinefevervirusreplication AT xiaomengli traf6isanovelns3interactingproteinthatinhibitsclassicalswinefevervirusreplication AT jiewang traf6isanovelns3interactingproteinthatinhibitsclassicalswinefevervirusreplication AT guiqian traf6isanovelns3interactingproteinthatinhibitsclassicalswinefevervirusreplication AT qizhuanglv traf6isanovelns3interactingproteinthatinhibitsclassicalswinefevervirusreplication AT chengbaowang traf6isanovelns3interactingproteinthatinhibitsclassicalswinefevervirusreplication AT kangkangguo traf6isanovelns3interactingproteinthatinhibitsclassicalswinefevervirusreplication AT yanmingzhang traf6isanovelns3interactingproteinthatinhibitsclassicalswinefevervirusreplication
_version_	1718385154157707264

TRAF6 is a novel NS3-interacting protein that inhibits classical swine fever virus replication

Ejemplares similares