Porcine bocavirus NP1 negatively regulates interferon signaling pathway by targeting the DNA-binding domain of IRF9.
To subvert host antiviral immune responses, many viruses have evolved countermeasures to inhibit IFN signaling pathway. Porcine bocavirus (PBoV), a newly identified porcine parvovirus, has received attention because it shows clinically high co-infection prevalence with other pathogens in post-weaning multisystemic wasting syndrome (PWMS) and diarrheic piglets. In this study, we screened the structural and non-structural proteins encoded by PBoV and found that the non-structural protein NP1 significantly suppressed IFN-stimulated response element (ISRE) activity and subsequent IFN-stimulated gene (ISG) expression. However, NP1 affected neither the activation and translocation of STAT1/STAT2, nor the formation of the heterotrimeric transcription factor complex ISGF3 (STAT1/STAT2/IRF9). Detailed analysis demonstrated that PBoV NP1 blocked the ISGF3 DNA-binding activity by combining with the DNA-binding domain (DBD) of IRF9. In summary, these results indicate that PBoV NP1 interferes with type I IFN signaling pathway by blocking DNA binding of ISGF3 to attenuate innate immune responses.
State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China; The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China.
Ruoxi
R
Zhang
State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China; The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China. Electronic address: fanglr@mail.hzau.edu.cn.
Liurong
L
Fang
State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China; The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China.
Dang
D
Wang
State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China; The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China.
Kaimei
K
Cai
State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China; The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China.
Huan
H
Zhang
College of Life Science and Technology, Wuhan Institute of Bioengineering, Wuhan 430415, China.
Lilan
L
Xie
College of Life Science and Technology, Wuhan Institute of Bioengineering, Wuhan 430415, China.
Yi
Y
Li
State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China; The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China.
Huanchun
H
Chen
State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China; The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China.
Shaobo
S
Xiao
D021581:Active Transport, Cell Nucleus; D000818:Animals; D052660:Bocavirus / Q000502:physiology*; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D006801:Humans; D050832:Interferon-Stimulated Gene Factor 3 / Q000378:metabolism; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit / Q000737:chemistry / Q000378:metabolism*; D007372:Interferons / Q000378:metabolism*; D008954:Models, Biological; D010766:Phosphorylation; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D050794:STAT1 Transcription Factor / Q000378:metabolism; D050795:STAT2 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D013552:Swine; D017361:Viral Nonstructural Proteins / Q000378:metabolism*
D050832:Interferon-Stimulated Gene Factor 3; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D050794:STAT1 Transcription Factor; D050795:STAT2 Transcription Factor; D017361:Viral Nonstructural Proteins; D004247:DNA; D007372:Interferons
Non-structural protein NP1; Porcine bocavirus (PBoV); Type I IFN signaling