Gut:原代肝细胞增殖和预防HBV再感染有效地消耗体内细胞核内cccDNA!

2017-04-21 xing.T MedSci原创

该研究的结果证明人类肝细胞分化甚至没有涉及到杀伤机制就触发了大量的cccDNA的损失。这个过程可能是解决自限性急性感染的基础,并在在未来的治疗干预措施中应予以考虑。

在非分裂肝细胞的细胞核内共价闭合环状DNA(cccDNA)的稳定性是持续感染的关键因素。相反,嗜肝病毒动物研究表明,肝细胞更新可以降低cccDNA载量,但对于HBV感染的原代肝细胞(PHHs)在体内增殖能力和分裂的PHHs中cccDNA的命运如何仍然缺乏认识。近日,消化病领域权威杂志Gut上发表了一篇研究文章,研究人员旨在确定人类肝细胞分化对体内cccDNA稳定性的影响。

通过将HBV感染的人源化小鼠的肝细胞连续移植至裸鼠引发PHH增殖,细胞增殖和病毒学变化是通过定量PCR、免疫荧光和RNA原位杂交来进行评估,凝胶分离和深度测序分析病毒整合。

PHH的增殖显著降低了所有感染标志物,包括cccDNA(中位数为2.4对数/PHH)。值得注意的是细胞分裂明显的造成子代细胞cccDNA稀释和肝内cccDNA的损耗。然而,HBV存活在零星的非增殖的人肝细胞中,当肝细胞扩张减缓时病毒学标记会反弹。这是由于增加了静止的PHHs,因为接受Myrcludex-B抑制剂或核苷类似物治疗阻断了病毒传播和肝内cccDNA的积累。在供体和受体小鼠中均检测到了病毒整合,但并没有发现促进抗原生产。

该研究的结果证明人类肝细胞分化甚至没有涉及到杀伤机制就触发了大量的cccDNA的损失。这个过程可能是解决自限性急性感染的基础,并在在未来的治疗干预措施中应予以考虑。

原始出处:


Lena Allweiss,et al. Proliferation of primary human hepatocytes and prevention of hepatitis B virus reinfection efficiently deplete nuclear cccDNA in vivo. Gut. 2017. http://dx.doi.org/10.1136/gutjnl-2016-312162

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    2017-06-24 xjy02
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    2017-05-02 klivis
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    2017-05-01 1e10c84am36(暂无匿称)

    文章很好,拜读了

    0

  4. 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createdTime=Sun Apr 30 11:53:54 CST 2017, time=2017-04-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=191512, encodeId=2e8c1915128c, content=学习了,谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=28761705280, createdName=cuiyejia, createdTime=Fri Apr 28 15:07:07 CST 2017, time=2017-04-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=189800, encodeId=8a3c189800ee, content=认真学习,把间接经验应用到临床实践中去,然后再总结出新思路。点赞啦!, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo7s7ZCKOmmbBTD6nE7gcd5OZpvyGEzkxBP3S275k5ZJVrsPkotZhBglRHM9rKvcj1OgkssqhcnoPw8zIaMZTF8c/0, createdBy=4c441942088, createdName=ylzr123, createdTime=Sun 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attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8e886, createdName=仁者大医, createdTime=Sun Apr 23 06:07:00 CST 2017, time=2017-04-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1603597, encodeId=6748160359e16, content=<a href='/topic/show?id=3831e7930d9' target=_blank style='color:#2F92EE;'>#细胞核#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77930, encryptionId=3831e7930d9, topicName=细胞核)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=52c219056124, createdName=ying_wu, createdTime=Sun Apr 23 06:07:00 CST 2017, time=2017-04-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=189574, encodeId=9a9c1895e4c5, content=学习了谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=/v1.0.0/img/user_icon.png, createdBy=74221626377, createdName=tofsw, createdTime=Sat Apr 22 08:06:31 CST 2017, time=2017-04-22, status=1, ipAttribution=)]
    2017-04-30 cuiyejia

    学习了,谢谢分享

    0

  5. 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attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8e886, createdName=仁者大医, createdTime=Sun Apr 23 06:07:00 CST 2017, time=2017-04-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1603597, encodeId=6748160359e16, content=<a href='/topic/show?id=3831e7930d9' target=_blank style='color:#2F92EE;'>#细胞核#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77930, encryptionId=3831e7930d9, topicName=细胞核)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=52c219056124, createdName=ying_wu, createdTime=Sun Apr 23 06:07:00 CST 2017, time=2017-04-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=189574, encodeId=9a9c1895e4c5, content=学习了谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=/v1.0.0/img/user_icon.png, createdBy=74221626377, createdName=tofsw, createdTime=Sat Apr 22 08:06:31 CST 2017, time=2017-04-22, status=1, ipAttribution=)]
    2017-04-28 cuiyejia

    学习了,谢谢分享

    0

  6. 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createdTime=Sun Apr 30 11:53:54 CST 2017, time=2017-04-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=191512, encodeId=2e8c1915128c, content=学习了,谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=28761705280, createdName=cuiyejia, createdTime=Fri Apr 28 15:07:07 CST 2017, time=2017-04-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=189800, encodeId=8a3c189800ee, content=认真学习,把间接经验应用到临床实践中去,然后再总结出新思路。点赞啦!, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo7s7ZCKOmmbBTD6nE7gcd5OZpvyGEzkxBP3S275k5ZJVrsPkotZhBglRHM9rKvcj1OgkssqhcnoPw8zIaMZTF8c/0, createdBy=4c441942088, createdName=ylzr123, createdTime=Sun 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attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8e886, createdName=仁者大医, createdTime=Sun Apr 23 06:07:00 CST 2017, time=2017-04-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1603597, encodeId=6748160359e16, content=<a href='/topic/show?id=3831e7930d9' target=_blank style='color:#2F92EE;'>#细胞核#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77930, encryptionId=3831e7930d9, topicName=细胞核)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=52c219056124, createdName=ying_wu, createdTime=Sun Apr 23 06:07:00 CST 2017, time=2017-04-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=189574, encodeId=9a9c1895e4c5, content=学习了谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=/v1.0.0/img/user_icon.png, createdBy=74221626377, createdName=tofsw, createdTime=Sat Apr 22 08:06:31 CST 2017, time=2017-04-22, status=1, ipAttribution=)]
    2017-04-23 ylzr123

    认真学习,把间接经验应用到临床实践中去,然后再总结出新思路。点赞啦!

    0

  7. 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createdTime=Sun Apr 30 11:53:54 CST 2017, time=2017-04-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=191512, encodeId=2e8c1915128c, content=学习了,谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=28761705280, createdName=cuiyejia, createdTime=Fri Apr 28 15:07:07 CST 2017, time=2017-04-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=189800, encodeId=8a3c189800ee, content=认真学习,把间接经验应用到临床实践中去,然后再总结出新思路。点赞啦!, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo7s7ZCKOmmbBTD6nE7gcd5OZpvyGEzkxBP3S275k5ZJVrsPkotZhBglRHM9rKvcj1OgkssqhcnoPw8zIaMZTF8c/0, createdBy=4c441942088, createdName=ylzr123, createdTime=Sun 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attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8e886, createdName=仁者大医, createdTime=Sun Apr 23 06:07:00 CST 2017, time=2017-04-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1603597, encodeId=6748160359e16, content=<a href='/topic/show?id=3831e7930d9' target=_blank style='color:#2F92EE;'>#细胞核#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77930, encryptionId=3831e7930d9, topicName=细胞核)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=52c219056124, createdName=ying_wu, createdTime=Sun Apr 23 06:07:00 CST 2017, time=2017-04-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=189574, encodeId=9a9c1895e4c5, content=学习了谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=/v1.0.0/img/user_icon.png, createdBy=74221626377, createdName=tofsw, createdTime=Sat Apr 22 08:06:31 CST 2017, time=2017-04-22, status=1, ipAttribution=)]
  8. 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  9. 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attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8e886, createdName=仁者大医, createdTime=Sun Apr 23 06:07:00 CST 2017, time=2017-04-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1603597, encodeId=6748160359e16, content=<a href='/topic/show?id=3831e7930d9' target=_blank style='color:#2F92EE;'>#细胞核#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77930, encryptionId=3831e7930d9, topicName=细胞核)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=52c219056124, createdName=ying_wu, createdTime=Sun Apr 23 06:07:00 CST 2017, time=2017-04-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=189574, encodeId=9a9c1895e4c5, content=学习了谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=/v1.0.0/img/user_icon.png, createdBy=74221626377, createdName=tofsw, createdTime=Sat Apr 22 08:06:31 CST 2017, time=2017-04-22, status=1, ipAttribution=)]
    2017-04-23 ying_wu
  10. 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attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8e886, createdName=仁者大医, createdTime=Sun Apr 23 06:07:00 CST 2017, time=2017-04-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1603597, encodeId=6748160359e16, content=<a href='/topic/show?id=3831e7930d9' target=_blank style='color:#2F92EE;'>#细胞核#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77930, encryptionId=3831e7930d9, topicName=细胞核)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=52c219056124, createdName=ying_wu, createdTime=Sun Apr 23 06:07:00 CST 2017, time=2017-04-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=189574, encodeId=9a9c1895e4c5, content=学习了谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=/v1.0.0/img/user_icon.png, createdBy=74221626377, createdName=tofsw, createdTime=Sat Apr 22 08:06:31 CST 2017, time=2017-04-22, status=1, ipAttribution=)]
    2017-04-22 tofsw

    学习了谢谢分享

    0

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