Porcine reproductive and respiratory syndrome virus (PRRSV) up-regulates IL-15 through PKCβ1-TAK1-NF-κB signaling pathway.
Porcine reproductive and respiratory syndrome (PRRS) caused by PRRS virus (PRRSV) is one of the most important infectious diseases in swine industry. IL-15 is a pleiotropic cytokine and has been shown to be essential to transform NKs, CD8 T cells, and other cells of the immune systems into functional effectors. Here, we demonstrated that the broad-spectrum or conventional PKC inhibitors repressed PRRSV-induced IL-15 expression and NF-κB activation. Subsequently, we found that the PKCβ specific inhibitor inhibited PRRSV-induced IL-15 production, which was also confirmed by knock-down of PKCβ1, suggesting that PKCβ1 is involved in the PRRSV-induced IL-15 expression. In addition, we demonstrated that PRRSV activated NF-κB through PKCβ1-induced TAK1 activation. Finally, we demonstrated that PRRSV activated PKCβ1 dependent on the participation of TRIF and MAVS. These data indicate that PRRSV up-regulates IL-15 through TRIF/MAVS-PKCβ1-TAK1-NF-κB signaling pathway. These findings will provide new insights into the molecular mechanisms of IL-15 production induced by PRRSV.
State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing 100193, China; Department of Microbiology and Immunology, College of Biological Sciences, China Agricultural University, Beijing 100193, China.
Li
L
Du
State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing 100193, China; Department of Microbiology and Immunology, College of Biological Sciences, China Agricultural University, Beijing 100193, China.
Yihao
Y
Liu
State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing 100193, China; Department of Microbiology and Immunology, College of Biological Sciences, China Agricultural University, Beijing 100193, China.
Yinping
Y
Du
State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing 100193, China; Department of Microbiology and Immunology, College of Biological Sciences, China Agricultural University, Beijing 100193, China.
Honglei
H
Wang
Shandong Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Sangyuan Road No. 8, Jinan 250100, China.
Meijie
M
Zhang
Shandong Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Sangyuan Road No. 8, Jinan 250100, China. Electronic address: duyijun0916@163.com.
Yijun
Y
Du
State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing 100193, China; Department of Microbiology and Immunology, College of Biological Sciences, China Agricultural University, Beijing 100193, China. Electronic address: whfeng@cau.edu.cn.
Wen-Hai
WH
Feng
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D015870:Gene Expression; D017930:Genes, Reporter; D019409:Interleukin-15 / Q000235:genetics / Q000378:metabolism*; D020930:MAP Kinase Kinase Kinases / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D009154:Mutation; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D019318:Porcine Reproductive and Respiratory Syndrome / Q000235:genetics / Q000378:metabolism* / Q000821:virology*; D019316:Porcine respiratory and reproductive syndrome virus / Q000502:physiology*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D064546:Protein Kinase C beta / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013552:Swine; D000099151:MAP Kinase Kinase Kinase 7
D048868:Adaptor Proteins, Signal Transducing; D019409:Interleukin-15; D020930:MAP Kinase Kinase Kinases; D016328:NF-kappa B; D064546:Protein Kinase C beta; D000099151:MAP Kinase Kinase Kinase 7
IL-15; NF-κB; PKCβ1; PRRSV; TAK1