JI:人博卡病毒拮抗宿主天然免疫研究进展

近期，国际免疫学重要期刊The Journal of Immunology（2012 189:1144）刊登了中科院武汉病毒研究所王汉中研究员学科组的研究论文，文章介绍了该学科组在人博卡病毒（Human bocavirus，简称HBoV）拮抗宿主天然免疫反应机制研究中取得的重要进展。

HBoV是2005年发现的一种新型人类细小病毒，主要感染对象为婴幼儿。HBoV阳性的婴幼儿常伴随有呼吸道疾病或者肠道疾病，但是目前尚没有直接证据表明HBoV是致病原因。宿主天然系统在抑制病毒复制和清除病毒的过程中具有重要作用，而很多病毒都具有拮抗宿主天然免疫系统的能力，这种拮抗作用通常对病毒的感染和致病至关重要。

本文首次报道了HBoV非结构蛋白NP1能够抑制宿主天然免疫反应。主要机制为：NP1与干扰素生成过程中的重要调控因子IRF-3相互作用，封闭其DNA结合域，干扰IRF-3与干扰素启动子区的结合，进而抑制干扰素的生成。

本研究揭示了HBoV调控宿主免疫系统的新机制，为阐明HBoV在人类疾病发生中的潜在作用提供了理论依据。

该研究得到了973项目和国家自然科学基金的大力支持。

doi: 10.4049/jimmunol.1200096

PMC:
PMID:

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.