Porcine bocavirus NP1 negatively regulates interferon signaling pathway by targeting the DNA-binding domain of IRF9

Virology
Ruoxi ZhangShaobo Xiao

Abstract

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.

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Citations

Apr 19, 2018·MBio·Simon H WilliamsW Ian Lipkin
Aug 28, 2018·Frontiers in Immunology·Alvin PaulSiew Kit Ng
Jan 24, 2019·Frontiers in Immunology·Hao-Sen Chiang, Helene Minyi Liu
Aug 28, 2020·Journal of Virology·Angela R Harrison, Gregory W Moseley
May 4, 2021·Frontiers in Immunology·Ritu Mishra, Akhil C Banerjea

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Datasets Mentioned

BETA
HQ223038

Methods Mentioned

BETA
nuclear translocation
immunoprecipitation
ChIP
PCR
Co-IP
co-immunoprecipitation
Assay
transfection

Software Mentioned

Fluoview

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