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Cell Host Microbe：I型干扰素b的病毒清除机制研究

2015-05-18 佚名 生物谷

I型干扰素b病毒
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I型干扰素在宿主抵抗微生物感染的先天免疫与后天免疫过程中都具有重要的作用。包括控制病原体的状态，调节先天免疫反应，激活后天免疫反应等等。尽管如此，一些研究发现I型干扰素能够提高感染的严重程度。之前的研究发现I型干扰素的阻断能够促进病毒感染后的清除，而这一效应主要是通过营造免疫抑制的环境实现的，主要包括：1、促进一些负向调控因子，如IL-10，PD-1的产生；2、破坏脾脏的结构；3，抑制淋巴细胞

I型干扰素在宿主抵抗微生物感染的先天免疫与后天免疫过程中都具有重要的作用。包括控制病原体的状态，调节先天免疫反应，激活后天免疫反应等等。尽管如此，一些研究发现I型干扰素能够提高感染的严重程度。之前的研究发现I型干扰素的阻断能够促进病毒感染后的清除，而这一效应主要是通过营造免疫抑制的环境实现的，主要包括：1、促进一些负向调控因子，如IL-10，PD-1的产生；2、破坏脾脏的结构；3，抑制淋巴细胞向脾脏的迁移。然而，目前对于哪一类I型干扰素具有这一功能仍不清楚。

I型干扰素家族主要包括两类成员： IFN-a与IFN-b, 另外还有IFN-e，IFN-w，等等。这些因子的下游受体都是由IFNAR1与IFNAR2组成的异源二聚体。尽管如此，由于它们与受体的作用机制不同，引起的下游信号也存在差异。
 
在最近的一项研究中，来自华盛顿大学医学院的Michael B.A. Oldstone课题组报道了不同亚型的I型干扰素在病毒感染过程中的调节作用，相关研究发表在《cell hostµbe》杂志上。
 
首先，作者比较了野生型小鼠，IFN-b缺失突变小鼠（IFN-b-/-）以及IFN受体缺失突变小鼠（IFN-a-/-）在受到LCMV感染时的病毒增殖能力。结果显示，IFN-b-/-小鼠相比于野生型小鼠，其病毒感染后24小时的增殖能力并没有明显区别。而IFN-a-/-小鼠的病毒载量相比其它两组明显提高。这说明IFN-b在病毒感染早期并不能起到抑制的效果。
 
由于LCMV的感染会破坏淋巴结的结构并影响淋巴细胞的迁移。作者希望了解是否IFN参与这一过程。通过特异性抗体分别对IFNAR1与IFN-b进行阻断，通过荧光成像的手段，作者发现两种阻断方式均能很好地保护脾脏结构免受破坏。这一结果说明IFN-b可能具有柏怀淋巴结结构的作用。
 
之前的研究利用抗体阻断IFNAR1，发现在LCMV感染第5天及第9天后能够提高CD4+ 效应T细胞的水平，然而CD8+T细胞的水平并不受影响。在本次研究中，作者利用抗体阻断了IFN-b的功能，结果发现在感染9天之后CD4+T细胞与CD8+T细胞的水平均得到明显升高。此前在IFNAR1阻断方面的研究中发现是由于IL-10，PD-1等免疫抑制因子的下降引起了上述结果，而此次的研究中并没有发现IL-10或PD-1在IFN-b阻断后发生表达下降的现象。
 
为了研究IFN-b的这种特性是否影响了宿主对病毒的清除。作者分别对小鼠进行IFN-b或IFN-a的阻断，并进行LCMV的感染。之后在一段时间内连续监测血清中病毒载量。在早期阶段，单独阻断IFN-a或IFN-b均不能起到抑制病毒载量的效果，然而在感染30天后，IFN-b的阻断起到了与IFNAR1阻断一样的效果，而IFN-a的阻断则没有效果。
 
以上结果说明IFN-b在病毒感染的后期能够控制病毒的载量，但有可能会对自身淋巴体统造成一些负面影响。

原始出处：

Cherie T. Ng, Brian M. Sullivan, John R. Teijaro, Andrew M. Lee, Megan Welch, Stephanie Rice, Kathleen C.F. Sheehan, Robert D. Schreiber, Michael B.A. Oldstone.Blockade of Interferon Beta, but Not Interferon Alpha, Signaling Controls Persistent Viral Infection.Cell Host & Microbe, March 19, 2015.DOI: http://dx.doi.org/10.1016/j.chom.2015.04.005

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    2015-10-22 xjy02

    #Micro#

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    2015-07-25 hbwxf

    #机制研究#

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    2016-04-26 zhaozhouchifen

    #Cell#

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    2016-03-29 维他命

    #CEL#

    0

  5. [GetPortalCommentsPageByObjectIdResponse(id=2084127, encodeId=d6fd208412e47, content=<a href='/topic/show?id=61f411e013b' target=_blank style='color:#2F92EE;'>#Micro#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=22, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11701, encryptionId=61f411e013b, topicName=Micro)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d59291, createdName=xjy02, createdTime=Thu Oct 22 23:05:00 CST 2015, time=2015-10-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2056129, encodeId=7efe2056129b6, content=<a href='/topic/show?id=616b611e9bc' target=_blank style='color:#2F92EE;'>#机制研究#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=61179, encryptionId=616b611e9bc, topicName=机制研究)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=55ce62, createdName=hbwxf, createdTime=Sat Jul 25 14:05:00 CST 2015, time=2015-07-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1869118, encodeId=3d041869118be, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Tue Apr 26 17:05:00 CST 2016, time=2016-04-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1959371, encodeId=beb019593e1eb, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, createdName=维他命, createdTime=Tue Mar 29 20:05:00 CST 2016, time=2016-03-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1857352, encodeId=a002185e35234, content=<a href='/topic/show?id=3f48525849' target=_blank style='color:#2F92EE;'>#CRO#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5258, encryptionId=3f48525849, topicName=CRO)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c30265, createdName=jiafufeng@yaho, createdTime=Sat Aug 29 06:05:00 CST 2015, time=2015-08-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1318215, encodeId=337b1318215dc, content=<a href='/topic/show?id=685a101e4f8' target=_blank style='color:#2F92EE;'>#I型干扰素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10174, encryptionId=685a101e4f8, topicName=I型干扰素)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=3307462, createdName=风铃821, createdTime=Wed May 20 00:05:00 CST 2015, time=2015-05-20, status=1, ipAttribution=)]
    2015-08-29 jiafufeng@yaho

    #CRO#

    0

  6. [GetPortalCommentsPageByObjectIdResponse(id=2084127, encodeId=d6fd208412e47, content=<a href='/topic/show?id=61f411e013b' target=_blank style='color:#2F92EE;'>#Micro#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=22, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11701, encryptionId=61f411e013b, topicName=Micro)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d59291, createdName=xjy02, createdTime=Thu Oct 22 23:05:00 CST 2015, time=2015-10-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2056129, encodeId=7efe2056129b6, content=<a href='/topic/show?id=616b611e9bc' target=_blank style='color:#2F92EE;'>#机制研究#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=61179, encryptionId=616b611e9bc, topicName=机制研究)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=55ce62, createdName=hbwxf, createdTime=Sat Jul 25 14:05:00 CST 2015, time=2015-07-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1869118, encodeId=3d041869118be, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Tue Apr 26 17:05:00 CST 2016, time=2016-04-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1959371, encodeId=beb019593e1eb, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, createdName=维他命, createdTime=Tue Mar 29 20:05:00 CST 2016, time=2016-03-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1857352, encodeId=a002185e35234, content=<a href='/topic/show?id=3f48525849' target=_blank style='color:#2F92EE;'>#CRO#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5258, encryptionId=3f48525849, topicName=CRO)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c30265, createdName=jiafufeng@yaho, createdTime=Sat Aug 29 06:05:00 CST 2015, time=2015-08-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1318215, encodeId=337b1318215dc, content=<a href='/topic/show?id=685a101e4f8' target=_blank style='color:#2F92EE;'>#I型干扰素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10174, encryptionId=685a101e4f8, topicName=I型干扰素)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=3307462, createdName=风铃821, createdTime=Wed May 20 00:05:00 CST 2015, time=2015-05-20, status=1, ipAttribution=)]
    2015-05-20 风铃821

    #I型干扰素#

    0