新研究：腸病毒D68 VP3靶向干擾素調(diào)節(jié)因子7抑制I型干擾素應(yīng)答

2023年6月，中國(guó)天津大學(xué)生命科學(xué)學(xué)院;天津市生物大分子結(jié)構(gòu)功能與應(yīng)用重點(diǎn)實(shí)驗(yàn)室研究所;天津大學(xué)環(huán)境科學(xué)與工程學(xué)院(School of Life Sciences, Tianjin University, Tianjin, China；Institute of Tianjin Key Laboratory of Function and Application of Biological Macromolecular Structures, Tianjin, China；School of Environmental Science and Engineering, Tianjin University, Tianjin, China) Jun Kang老師研究團(tuán)隊(duì)在《MICROBIOL SPECTR》上發(fā)表論文：

“Enterovirus D68 VP3 Targets the Interferon Regulatory Factor 7 To Inhibit Type I Interferon Response"

“腸病毒D68 VP3靶向干擾素調(diào)節(jié)因子7抑制I型干擾素應(yīng)答"

Abstract：

Enterovirus D68 (EV-D68) is a globally emerging pathogen causing severe respiratory illnesses mainly in children. The protease from EV-D68 could impair type I interferon (IFN-I) production. However, the role of the EV-D68 structural protein in antagonizing host antiviral responses remains largely unknown. We showed that the EV-D68 structural protein VP3 interacted with IFN regulatory factor 7 (IRF7), and this interaction suppressed the phosphorylation and nuclear translocation of IRF7 and then repressed the transcription of IFN. Furthermore, VP3 inhibited the TNF receptor associated factor 6 (TRAF6)-induced ubiquitination of IRF7 by competitive interaction with IRF7. IRF7Δ305-503 showed much weaker interaction ability to VP3, and VP3Δ41-50 performed weaker interaction ability with IRF7. The VP3 from enterovirus A71 (EV-A71) and coxsackievirus A16 (CV-A16) was also found to interact with the IRF7 protein. These results indicate that the enterovirus structural protein VP3 plays a pivotal role in subverting host innate immune responses and may be a potential target for antiviral drug research. IMPORTANCE EV-D68 is a globally emerging pathogen that causes severe respiratory illnesses. Here, we report that EV-D68 inhibits innate immune responses by targeting IRF7. Further investigations revealed that the structural protein VP3 inhibited the TRAF6-induced ubiquitination of IRF7 by competitive interaction with IRF7. These results indicate that the control of IRF7 by VP3 may be a mechanism by which EV-D68 represses IFN-I production.

摘要：

腸病毒D68 (EV-D68)是一種全球新發(fā)病原體，主要在兒童中引起嚴(yán)重呼吸道疾病。EV-D68的蛋白酶可以抑制I型干擾素(IFN-I)的產(chǎn)生。然而，EV-D68結(jié)構(gòu)蛋白在拮抗宿主抗病毒反應(yīng)中的作用在很大程度上仍然未知。研究人員發(fā)現(xiàn)EV-D68結(jié)構(gòu)蛋白VP3與IFN調(diào)控因子7 (IRF7)相互作用，抑制IRF7的磷酸化和核易位，進(jìn)而抑制IFN的轉(zhuǎn)錄。此外，VP3通過(guò)與IRF7的競(jìng)爭(zhēng)性相互作用抑制TNF受體相關(guān)因子6 (TRAF6)誘導(dǎo)的IRF7泛素化。IRF7Δ305-503與VP3的互作能力弱得多，VP3Δ41-50與IRF7的互作能力弱得多。來(lái)自腸病毒A71 (EV-A71)和柯薩奇病毒A16 (CV-A16)的VP3也被發(fā)現(xiàn)與IRF7蛋白相互作用。這些結(jié)果表明，腸道病毒結(jié)構(gòu)蛋白VP3在破壞宿主先天免疫應(yīng)答中起著關(guān)鍵作用，可能是抗病毒的藥物研究的潛在靶點(diǎn)。EV-D68是一種全球新發(fā)病原體，可引起嚴(yán)重呼吸道疾病。在這里，研究人員報(bào)道EV-D68通過(guò)靶向IRF7抑制先天免疫反應(yīng)。進(jìn)一步研究發(fā)現(xiàn)，結(jié)構(gòu)蛋白VP3通過(guò)與IRF7的競(jìng)爭(zhēng)相互作用抑制traf6誘導(dǎo)的IRF7泛素化。這些結(jié)果表明VP3對(duì)IRF7的控制可能是EV-D68抑制IFN-I產(chǎn)生的機(jī)制之一。

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