J Virol：武汉病毒所揭示人巨细胞病毒致神经损伤机制

2018-07-19 佚名武汉病毒所

近日，中国科学院武汉病毒研究所罗敏华课题组在人巨细胞病毒(HCMV)致神经损伤机制方面取得新进展，发现HCMV感染神经前体细胞时显着下调其重要标志分子SOX2(性别决定因子)，并且是由其立即早期蛋白IE1通过促进STAT3(信号传导及转录激活因子)的细胞核内积累以及抑制STAT3的磷酸化来实现对SOX2的下调。该工作在线发表于《病毒学杂志》（Journal of Virology）。

近日，中国科学院武汉病毒研究所罗敏华课题组在人巨细胞病毒(HCMV)致神经损伤机制方面取得新进展，发现HCMV感染神经前体细胞时显着下调其重要标志分子SOX2(性别决定因子)，并且是由其立即早期蛋白IE1通过促进STAT3(信号传导及转录激活因子)的细胞核内积累以及抑制STAT3的磷酸化来实现对SOX2的下调。该工作在线发表于《病毒学杂志》（Journal of Virology）。

人巨细胞病毒（Human Cytomegalovirus，HCMV）是一种人群感染率极高的病毒。先天性HCMV感染是引起新生儿出生缺陷最常见的感染性病因，主要表现为中枢神经系统（CNS）的发育损伤。在胚胎发育中，人神经干细胞（neural progenitorcell，NPC）是胎脑神经细胞增殖分化的根本和胎脑发育的基础，对HMCV的感染非常敏感。SOX2作为维持干细胞多能性和自我更新最重要的转录因子之一，在决定NPC细胞命运上起到了最重要的作用，阐明SOX2是否在HCMV感染NPCs时被调控成为该研究的初始着眼点。

该研究发现，在HCMV感染NPC的过程中，干细胞主转录调控因子SOX2的表达在信使RNA和蛋白水平均有明显下调。在病毒感染时加入蛋白质合成抑制剂CHX抑制了SOX2的下调，用紫外线灭活的病毒感染不影响SOX2的表达，证明SOX2的下调需要活病毒感染和病毒蛋白的重新合成。随后发现IE1可明显下调SOX2的表达水平，用IE1缺失病毒感染NPCs得到了进一步证实。通过过表达IE1、核质分离等实验，最终证明了IE1一方面通过抑制STAT3磷酸化水平，从而降低SOX2转录；另一方面，非磷酸化的STAT3在IE1的驱动下进入细胞核，可能与p-STAT3(磷酸化信号传导及转录激活因子)竞争SOX2启动子位点等，抑制SOX2的转录，降低SOX2的表达。

该研究工作揭示了HCMV感染中，IE1通过调控STAT3的非正常迁移和磷酸化，下调SOX2的表达，改变NPCs的命运。该研究首次鉴定了在下调SOX2中起重要作用的病毒成分，旨在为进一步探讨先天性HCMV感染致胎儿中枢神经系统畸形机制提供思路。

武汉病毒所神经病毒学科组硕士吴琮琮、博士后姜旋和博士生王冼章为共同第一作者，罗敏华和英国圣安德鲁斯大学教授Michael Nevels为共同通讯作者。该研究获得了国家自然科学基金（81620108021，31170155，和81427801）、国家重点基础研究发展规划（973计划）（2015CB755600）、中科院中非中心（SAJC201605）等的支持。

HCMV感染神经干细胞下调SOX2的mRNA和蛋白水平

立即早期蛋白IE1通过调控STAT3的磷酸化和定位过程来下调SOX2的水平

原始出处：

Wu CC, Jiang X, Wang XZ,et al.Human Cytomegalovirus Immediate-Early 1 Protein Causes Loss of SOX2 from Neural Progenitor Cells by Trapping Unphosphorylated STAT3 in the Nucleus.J Virol. 2018 Jun 27. pii: JVI.00340-18. doi: 10.1128/JVI.00340-18. [Epub ahead of print]

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2019-03-18 ms3892185887221420

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2019-06-25 juliusluan88

#人巨细胞病毒#

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topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2017/09/07/a9772c74ffd6edc03a7f9af07b4747f6.jpg, createdBy=b3722138742, createdName=sunfeifeiyang, createdTime=Fri Jul 20 06:51:54 CST 2018, time=2018-07-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=332824, encodeId=f354332824f0, content=好好好好好好好好, beContent=null, objectType=article, channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2017/08/29/bbc5cc0eed9b8d17623d2fd49dbdf19a.jpg, createdBy=79522135794, createdName=yjs木玉, createdTime=Fri Jul 20 05:52:02 CST 2018, time=2018-07-20, status=1, ipAttribution=)]
2018-07-21 ms3046638856685384

#损伤#

29 0
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topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2017/09/07/a9772c74ffd6edc03a7f9af07b4747f6.jpg, createdBy=b3722138742, createdName=sunfeifeiyang, createdTime=Fri Jul 20 06:51:54 CST 2018, time=2018-07-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=332824, encodeId=f354332824f0, content=好好好好好好好好, beContent=null, objectType=article, channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2017/08/29/bbc5cc0eed9b8d17623d2fd49dbdf19a.jpg, createdBy=79522135794, createdName=yjs木玉, createdTime=Fri Jul 20 05:52:02 CST 2018, time=2018-07-20, status=1, ipAttribution=)]
2018-07-21 wwzzly

#巨细胞#

32 0
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topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2017/09/07/a9772c74ffd6edc03a7f9af07b4747f6.jpg, createdBy=b3722138742, createdName=sunfeifeiyang, createdTime=Fri Jul 20 06:51:54 CST 2018, time=2018-07-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=332824, encodeId=f354332824f0, content=好好好好好好好好, beContent=null, objectType=article, channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2017/08/29/bbc5cc0eed9b8d17623d2fd49dbdf19a.jpg, createdBy=79522135794, createdName=yjs木玉, createdTime=Fri Jul 20 05:52:02 CST 2018, time=2018-07-20, status=1, ipAttribution=)]
2018-07-21 LShY0906_98743849

#神经损伤#

26 0
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topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2017/09/07/a9772c74ffd6edc03a7f9af07b4747f6.jpg, createdBy=b3722138742, createdName=sunfeifeiyang, createdTime=Fri Jul 20 06:51:54 CST 2018, time=2018-07-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=332824, encodeId=f354332824f0, content=好好好好好好好好, beContent=null, objectType=article, channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2017/08/29/bbc5cc0eed9b8d17623d2fd49dbdf19a.jpg, createdBy=79522135794, createdName=yjs木玉, createdTime=Fri Jul 20 05:52:02 CST 2018, time=2018-07-20, status=1, ipAttribution=)]
2018-07-21 heli0118

#武汉病毒所#

0 0
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2018-07-20 龙胆草

学习谢谢分享

67 0
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topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2017/09/07/a9772c74ffd6edc03a7f9af07b4747f6.jpg, createdBy=b3722138742, createdName=sunfeifeiyang, createdTime=Fri Jul 20 06:51:54 CST 2018, time=2018-07-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=332824, encodeId=f354332824f0, content=好好好好好好好好, beContent=null, objectType=article, channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2017/08/29/bbc5cc0eed9b8d17623d2fd49dbdf19a.jpg, createdBy=79522135794, createdName=yjs木玉, createdTime=Fri Jul 20 05:52:02 CST 2018, time=2018-07-20, status=1, ipAttribution=)]
2018-07-20 liumin1987

人巨细胞病毒导致神经损伤的机制研究。

66 0
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2018-07-20 sunfeifeiyang

阅

66 0
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topicList=[TopicDto(id=24890, encryptionId=431524890f8, topicName=人巨细胞病毒)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=2c8030768069, createdName=juliusluan88, createdTime=Tue Jun 25 08:02:00 CST 2019, time=2019-06-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1397588, encodeId=e0cc139e5882b, content=<a href='/topic/show?id=8bee565436d' target=_blank style='color:#2F92EE;'>#损伤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=56543, encryptionId=8bee565436d, topicName=损伤)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/DYAIOgq83eoNX3lUOlDKGBUEPNwZx0nibmdcFyeibnX4WMhUSCU2REpGRWtSmnT2CCs0dA5waxvJknYDxwtYnIcQ/132, createdBy=294e2500218, createdName=ms3046638856685384, createdTime=Sat Jul 21 13:02:00 CST 2018, time=2018-07-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1502227, encodeId=05ad150222e1b, content=<a href='/topic/show?id=021d4821096' target=_blank style='color:#2F92EE;'>#巨细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=48210, encryptionId=021d4821096, topicName=巨细胞)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=11759518880, createdName=wwzzly, createdTime=Sat Jul 21 13:02:00 CST 2018, time=2018-07-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1584290, encodeId=c8ae158429027, content=<a href='/topic/show?id=ee6de4320c6' target=_blank style='color:#2F92EE;'>#神经损伤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=74320, encryptionId=ee6de4320c6, topicName=神经损伤)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=771e17042997, createdName=LShY0906_98743849, createdTime=Sat Jul 21 13:02:00 CST 2018, time=2018-07-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1620419, encodeId=4527162041933, content=<a href='/topic/show?id=919f6333047' target=_blank style='color:#2F92EE;'>#武汉病毒所#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=63330, encryptionId=919f6333047, topicName=武汉病毒所)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=21015, createdName=heli0118, createdTime=Sat Jul 21 13:02:00 CST 2018, time=2018-07-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=332894, encodeId=b8a23328947f, content=学习谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=67, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4Nd44v3xHnnictn9UpctwtH62EPQ59TMdI9lnqHMgQ16nH7GmGCfpzicsHgjibYVk6vwSpXrC86gMibRkoaIzf5HwSz7/0, createdBy=78cc1691107, createdName=龙胆草, createdTime=Fri Jul 20 08:21:23 CST 2018, time=2018-07-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=332865, encodeId=5ec933286598, content=人巨细胞病毒导致神经损伤的机制研究。, beContent=null, objectType=article, channel=null, level=null, likeNumber=66, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2018/07/16/3b24606172648eea459125cb74754afe.jpg, createdBy=6c022216608, createdName=liumin1987, createdTime=Fri Jul 20 06:57:36 CST 2018, time=2018-07-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=332858, encodeId=08b53328581c, content=阅, beContent=null, objectType=article, channel=null, level=null, likeNumber=66, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2017/09/07/a9772c74ffd6edc03a7f9af07b4747f6.jpg, createdBy=b3722138742, createdName=sunfeifeiyang, createdTime=Fri Jul 20 06:51:54 CST 2018, time=2018-07-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=332824, encodeId=f354332824f0, content=好好好好好好好好, beContent=null, objectType=article, channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2017/08/29/bbc5cc0eed9b8d17623d2fd49dbdf19a.jpg, createdBy=79522135794, createdName=yjs木玉, createdTime=Fri Jul 20 05:52:02 CST 2018, time=2018-07-20, status=1, ipAttribution=)]
2018-07-20 yjs木玉

好好好好好好好好

56 0