Science:警惕!新冠病毒D614G突变株系复制能力和传播性更强!

2020-11-20 王木木 生物探索

截至目前,全球已有超过130万人因SARS-CoV-2导致的新冠肺炎死亡。令人担心的是,该病毒在人群中的传播流行还远未停止,随时可能会出现导致发病机理,致病力或传播能力改变的突变。

截至目前,全球已有超过130万人因SARS-CoV-2导致的新冠肺炎死亡。令人担心的是,该病毒在人群中的传播流行还远未停止,随时可能会出现导致发病机理,致病力或传播能力改变的突变。已有研究报道,目前流行的SARS-CoV-2中已广泛出现了D164G变体,其假型病毒在连续细胞系中的感染力更强,感染患者的上呼吸道病毒载量更高。

然而,D614G病毒株系在真实的SARS-CoV-2感染模型中的病毒复制,发病机理和传播性方面的功能仍未被评估,尚不清楚。

近日,来自美国北卡罗来纳大学、威斯康星大学的研究人员在《Science》上发表了题为SARS-CoV-2 D614G variant exhibits efficient replication ex vivo and transmission in vivo的研究成果,其证实了新型冠状病毒D614G突变株比疫情最初流行的病毒复制更快速,更易传播,但并不会导致更严重的疾病,且该突变株仍适用于当前开发的针对原始株系的抗体。

研究人员使用包含纳米荧光素酶(nLuc)的SARS-CoV-2的野生型(WT)和D614G突变株系感染了四个易感细胞系,测量了感染后的荧光素酶信号并比较其生长曲线,发现与WT相比,D614G感染力高约3.7至8.2倍,而在其中2个细胞系中的峰值滴度略低。

为了评估D614G变体在人呼吸道中的复制能力,研究人员比较了其在多个人体来源的人鼻黏膜上皮细胞(HNE)、气道上皮细胞(LAE)和小气道上皮细胞(SAE)中的生长动力学,发现,与WT相比,D614G病毒的感染复制竞争能力更强,可超出约10倍,且可以在HNE和LAE中高效复制。此外,研究人员还通过扫描和投射电镜及免疫印迹等实验,证明了活病毒中,D614G突变并未导致SARS-CoV-2形态,刺突裂解模式和体外中和反应特性发生明显改变。

D614G突变体传染性增强且可在人呼吸道上皮细胞中高效复制

为了进一步分析D614G株系在体内的发病机理和体内复制适应性,研究人员利用WT和D614G感染hACE2转基因小鼠和叙利亚仓鼠,检测其病毒滴度和组织病理情况,结果二者处理的小鼠和仓鼠的肺部病变大小和组织学严重程度均无显着差异。使用1:1比例混合的WT和D614G株系感染仓鼠后,检测到在其肺部D614G占据着主要地位,这也说明D614G突变让病毒在动物肺部具有更强的竞争力。

D614G突变未改变SARS-CoV-2病毒粒子形态、S蛋白裂解模式和对中和抗体的敏感性

D614G突变未影响hACE2小鼠的SARS-CoV-2发病机制

然后研究人员使用两种病毒分别感染8对仓鼠中的各一只,对D614G在空气中的传播速度进行分析,发现暴露于D614G感染组的8只未感染仓鼠中,有5只在第2天就被感染并检测到病毒脱落,而暴露于WT感染组的未感染小鼠则尚未被感染和病毒脱落。这表明,D614G比WT病毒的传输速度要快得多。

D614G突变增强了SARS-CoV-2在仓鼠中的传播力

D614G变体对当前针对WT而开发的疫苗的功效是否有影响是研究人员关注的另一个问题。其检测了两种病毒株系对25个恢复期的人血清和6个RBD结合单克隆抗体的总体等效敏感性,结果表明D614G突变不会明显改变SARS-CoV-2的中和特性,目前开发的针对WT的疫苗对D614G菌株仍有功效。

该研究的通讯作者Ralph S. Baric表示:“ SARS-CoV-2是一种全新的人类病原体,其在人类中的进化很难预测。而新的变种正在不断出现,我们必须继续追踪和了解这些新突变对疾病严重性,传播,宿主范围和疫苗诱导的免疫力的影响,最大限度地保护公共卫生安全。”

原始出处:

Yixuan J Hou, Shiho Chiba, Peter Halfmann, et al.SARS-CoV-2 D614G variant exhibits efficient replication ex vivo and transmission in vivo.Science. 2020 Nov 12;eabe8499. doi: 10.1126/science.abe8499.

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    2021-05-09 fusion
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    2020-11-22 jichang
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    2020-11-20 公卫新人

    新冠肺炎,疫情何时才能消失

    0

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    2020-11-20 ms7000000733200408

    好文章

    0

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    2020-11-20 ms9000001770292121

    首段的D164G突变株,是写错了吗?

    0

  6. [GetPortalCommentsPageByObjectIdResponse(id=1907359, encodeId=16c9190e3599d, content=<a href='/topic/show?id=a6c425886a9' target=_blank style='color:#2F92EE;'>#传播性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=25886, encryptionId=a6c425886a9, topicName=传播性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=743b215, createdName=fusion, createdTime=Sun May 09 00:40:47 CST 2021, time=2021-05-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1376209, encodeId=913b13e620951, content=<a href='/topic/show?id=2949159989d' target=_blank style='color:#2F92EE;'>#SCIE#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15998, encryptionId=2949159989d, topicName=SCIE)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=17a3387, createdName=jichang, createdTime=Sun Nov 22 06:40:47 CST 2020, time=2020-11-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1028799, encodeId=808b1028e99d5, content=新冠肺炎,疫情何时才能消失, beContent=null, objectType=article, channel=null, level=null, likeNumber=116, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=公卫新人, createdTime=Fri Nov 20 18:40:47 CST 2020, time=2020-11-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=900874, encodeId=64f49008e498, content=好文章, beContent=null, objectType=article, channel=null, level=null, likeNumber=186, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f5885436412, createdName=ms7000000733200408, createdTime=Fri Nov 20 18:37:36 CST 2020, time=2020-11-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=900838, encodeId=d48490083822, content=首段的D164G突变株,是写错了吗?, beContent=null, objectType=article, channel=null, level=null, likeNumber=197, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=01cd5431455, createdName=ms9000001770292121, createdTime=Fri Nov 20 16:32:31 CST 2020, time=2020-11-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=900826, encodeId=95af900826ba, content=谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=177, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a1145436843, createdName=huwarr, createdTime=Fri Nov 20 16:10:50 CST 2020, time=2020-11-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=900823, encodeId=1ca590082337, content=学习了,谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=173, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7c592194322, createdName=1209e435m98(暂无昵称), createdTime=Fri Nov 20 15:55:17 CST 2020, time=2020-11-20, status=1, ipAttribution=)]
    2020-11-20 huwarr

    谢谢分享

    0

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    2020-11-20 1209e435m98(暂无昵称)

    学习了,谢谢分享

    0

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