近期，國際免疫學(xué)重要期刊The Journal of Immunology（2012 189:1144）刊登了中科院武漢病毒研究所王漢中研究員學(xué)科組的研究論文,，文章介紹了該學(xué)科組在人博卡病毒（Human bocavirus,，簡稱HBoV）拮抗宿主天然免疫反應(yīng)機(jī)制研究中取得的重要進(jìn)展。
HBoV是2005年發(fā)現(xiàn)的一種新型人類細(xì)小病毒,，主要感染對象為嬰幼兒,。HBoV陽性的嬰幼兒常伴隨有呼吸道疾病或者腸道疾病，但是目前尚沒有直接證據(jù)表明HBoV是致病原因,。宿主天然系統(tǒng)在抑制病毒復(fù)制和清除病毒的過程中具有重要作用,，而很多病毒都具有拮抗宿主天然免疫系統(tǒng)的能力，這種拮抗作用通常對病毒的感染和致病至關(guān)重要,。
本文首次報(bào)道了HBoV非結(jié)構(gòu)蛋白NP1能夠抑制宿主天然免疫反應(yīng),。主要機(jī)制為：NP1與干擾素生成過程中的重要調(diào)控因子IRF-3相互作用，封閉其DNA結(jié)合域,，干擾IRF-3與干擾素啟動(dòng)子區(qū)的結(jié)合,，進(jìn)而抑制干擾素的生成。
本研究揭示了HBoV調(diào)控宿主免疫系統(tǒng)的新機(jī)制,，為闡明HBoV在人類疾病發(fā)生中的潛在作用提供了理論依據(jù),。
該研究得到了973項(xiàng)目和國家自然科學(xué)基金的大力支持。（生物谷Bioon.com）
doi: 10.4049/jimmunol.1200096
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Human Bocavirus NP1 Inhibits IFN-β Production by Blocking Association of IFN Regulatory Factor 3 with IFNB Promoter
Zhenfeng Zhang, Zhenhua Zheng, Huanle Luo, Jin Meng, Hongxia Li, Qian Li, Xiaowei Zhang, Xianliang Ke, Bingke Bai, Panyong Mao, Qinxue Hu and Hanzhong Wang
Human bocavirus (HBoV) mainly infects young children. Although many infected children suffer from respiratory or gastroenteric tract diseases, an association between HBoV and these diseases is not definite. Because modulation of type I IFN is crucial for viruses to establish efficient replication, in this study, we tested whether HBoV modulates type I IFN production. We observed that a nearly full-length HBoV clone significantly reduced both Sendai virus (SeV)- and poly(deoxyadenylic-thymidylic) acid-induced IFN-β production. Further study showed that NP1 blocked IFN-β activation in response to SeV, poly(deoxyadenylic-thymidylic) acid, and IFN-β pathway inducers, including retinoic acid-inducible protein I, mitochondrial antiviral signaling protein, inhibitor of κB kinase ε, and TANK-binding kinase 1. In addition, NP1 interfered with IRF-3–responsive PRD(III-I) promoter activated by SeV and a constitutively active mutant of IRF-3 (IRF-3/5D). Although NP1 suppressed the IRF-3 pathway, it did not affect IRF-3 activation processes, including phosphorylation, dimerization, and nuclear translocation. Coimmunoprecipitation assays confirmed the interaction between NP1 and IRF-3. Additional deletion mutagenesis and coimmunoprecipitation assays revealed that NP1 bound to the DNA-binding domain of IRF-3, resulting in the interruption of an association between IRF-3 and IFNB promoter. Altogether, our results indicate that HBoV NP1 blocks IFN production through a unique mechanism. To our knowledge, this is the first study to investigate the modulation of innate immunity by HBoV. Our findings suggest a potential immune-evasion mechanism used by HBoV and provide a basis for better understanding HBoV pathogenesis.
