Human Bocavirus NS1 and NS1-70 Proteins Inhibit TNF-α-Mediated Activation of NF-κB by targeting p65

• Published in: Scientific reports 2016-06, Vol.6 (1), p.28481-28481, Article 28481
• Main Authors: Liu, Qingshi, Zhang, Zhenfeng, Zheng, Zhenhua, Zheng, Caishang, Liu, Yan, Hu, Qinxue, Ke, Xianliang, Wang, Hanzhong
• Format: Article
• Language: English
• Subjects: 13/109; 38/22; 38/23; 38/77; 38/90; 631/250/2161; 631/326/596/2558; 82/1; Active Transport, Cell Nucleus; HEK293 Cells; Human bocavirus - genetics; Human bocavirus - immunology; Human bocavirus - pathogenicity; Humanities and Social Sciences; Humans; multidisciplinary; NF-kappa B - antagonists & inhibitors; NF-KappaB Inhibitor alpha - metabolism; Parvoviridae Infections - immunology; Parvoviridae Infections - virology; Phosphorylation; Proteolysis; Science; Science (multidisciplinary); Signal Transduction; Transcription Factor RelA - antagonists & inhibitors; Tumor Necrosis Factor-alpha - metabolism; Viral Nonstructural Proteins - genetics; Viral Nonstructural Proteins - immunology; Viral Nonstructural Proteins - physiology
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep28481

Human bocavirus (HBoV), a parvovirus, is a single-stranded DNA etiologic agent causing lower respiratory tract infections in young children worldwide. Nuclear factor kappa B (NF-κB) transcription factors play crucial roles in clearance of invading viruses through activation of many physiological processes. Previous investigation showed that HBoV infection could significantly upregulate the level of TNF-α which is a strong NF-κB stimulator. Here we investigated whether HBoV proteins modulate TNF-α–mediated activation of the NF-κB signaling pathway. We showed that HBoV NS1 and NS1-70 proteins blocked NF-κB activation in response to TNF-α. Overexpression of TNF receptor-associated factor 2 (TRAF2)-, IκB kinase alpha (IKKα)-, IκB kinase beta (IKKβ)-, constitutively active mutant of IKKβ (IKKβ SS/EE)-, or p65-induced NF-κB activation was inhibited by NS1 and NS1-70. Furthermore, NS1 and NS1-70 didn’t interfere with TNF-α-mediated IκBα phosphorylation and degradation, nor p65 nuclear translocation. Coimmunoprecipitation assays confirmed the interaction of both NS1 and NS1-70 with p65. Of note, NS1 but not NS1-70 inhibited TNF-α-mediated p65 phosphorylation at ser536. Our findings together indicate that HBoV NS1 and NS1-70 inhibit NF-κB activation. This is the first time that HBoV has been shown to inhibit NF-κB activation, revealing a potential immune-evasion mechanism that is likely important for HBoV pathogenesis.