Viruses:新冠病毒可藏匿于小鼠大脑,或能解释COVID-19患者康复后病情复发之谜

2021-01-25 探索菌 生物探索

凛冬已至,春节欲来。随着人员流动的增加,由新型冠状病毒(SARS-CoV-2)感染导致的新冠肺炎(COVID-19)疫情似乎变得更加严重,官方每日公布的COVID-19疫情数字牵动着每一个人的心!

凛冬已至,春节欲来。随着人员流动的增加,由新型冠状病毒(SARS-CoV-2)感染导致的新冠肺炎COVID-19)疫情似乎变得更加严重,官方每日公布的COVID-19疫情数字牵动着每一个人的心!

在全球科研人员的共同努力下,我们对SARS-CoV-2有了更深入的了解,但是关于其感染中枢神经系统(CNS)的发病机理仍然知之甚少。众所周知,大脑是人类的中央处理器,而COVID-19可引起人类神经系统疾病,探究其机理有助于人们更好地应对疫情、抵御疾病。

近日, Viruses发表了一篇题为Neuroinvasion and Encephalitis Following Intranasal Inoculation of SARS-CoV-2 in K18-hACE2 Mice的文章,发现SARS-CoV-2鼻内感染K18-hACE2转基因小鼠会引起严重的神经系统疾病。

鼻道通往大脑的路径比嘴巴更直接,且嗅觉和味觉的改变是COVID-19的症状之一,因此,研究人员在K18-hACE2小鼠(n=10)鼻腔内接种SARS-CoV-2细胞和PBS,感染SARS-CoV-2的小鼠在第4天开始体重明显减轻,并伴有嗜睡、动作缓慢、共济失调、呼吸困难等并发症,第6天小鼠全部死亡。这说明,SARS-CoV-2可能会感染K18-hACE2小鼠鼻甲,眼和嗅球内的细胞,并且某些COVID-19病例引起的嗅觉丧失的原因也得到了合理的解释。

SARS-CoV-2感染后K18-hACE2小鼠的存活,体重和病毒滴度分析

随后,研究人员基于qRT-PCR分析了感染SARS-CoV-2的小鼠的早期(第1天),中期(第3天)和晚期(第5和6天)器官和大脑的病毒载量。发现,在小鼠肺部和鼻腔的病毒量于第3天达到峰值,在第5天和第6天逐渐下降,而大脑中的病毒在第3天才被检测到,于第5天达到较高水平,且脑中的最高病毒滴度比肺中的最高滴度高约1000倍,表明SARS-CoV-2在脑中具有很高的复制潜力。

K18-hACE2小鼠的病毒嗜性分析

由于干扰素(IFN)具有广谱的抗病毒功能,能够影响细胞生长、分化、调节免疫功能等多种生物活性。在进一步实验中,研究人员检测了小鼠肺和脑中IFN-α的mRNA和蛋白水平,发现肺部IFN-α的mRNA和蛋白水平于第3天达到最高,在第6天下降,而大脑中仅在感染后第5天和第6天检测到高水平的IFN-α。有趣的是,尽管病毒在大脑中有较高的复制水平,但就IFN-α角度而言,肺中的相对水平更高。

肺和脑中干扰素-α(IFN-α)的mRNA和蛋白水平的分析

中枢神经系统的病毒感染通常伴随有炎症反应,如细胞因子/趋化因子的产生,研究人员基于qRT-PCR对IL-6、IL-1β、IFN-γ、TNF-α、CCL2和CCL3进行检测后发现,小鼠SARS-CoV-2感染细胞因子和趋化因子在大脑中的表达量远远超过肺中的表达量,表明在感染后期,炎症反应在大脑中比在肺部更为明显。

肺和脑中的细胞因子和趋化因子mRNA水平

在小鼠感染病毒的第6天,研究人员从大脑包括皮质、小脑和海马区的部位检测到了与细胞相关的病毒抗原。脑切片的HE染色结果及免疫组化学分析显示,小鼠的神经元缩小并出现退化现象,血管周围出血,白细胞浸润增强。这一发现恰好解释了为何某些COVID-19患者的肺功能已经得到改善,但却有可能迅速复发并死亡。

SARS-CoV-2感染的大脑的组织病理学分析

在K18-hACE2转基因小鼠的大脑中检测到SARS-CoV-2感染的细胞

由于大脑中不存在免疫反应,因此变成了病毒最喜欢藏身之地。尽管COVID-19康复患者似乎已经逃离SARS-CoV-2的魔掌,但依旧可能面临包括自身免疫性疾病、帕金森氏病、多发性硬化症和一般性认知能力下降等健康问题。因此,对待狡猾的SARS-CoV-2绝不能放松警惕。

原始出处:

Pratima Kumari, Hussin A Rothan, Janhavi P Natekar, et al.Neuroinvasion and Encephalitis Following Intranasal Inoculation of SARS-CoV-2 in K18-hACE2 Mice.Viruses. 2021 Jan 19;13(1):E132. doi: 10.3390/v13010132.

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    2021-01-27 dongjia2015
  5. [GetPortalCommentsPageByObjectIdResponse(id=1765131, encodeId=06fb1e65131ac, content=<a href='/topic/show?id=df00e086653' target=_blank style='color:#2F92EE;'>#病情#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=70866, encryptionId=df00e086653, topicName=病情)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=778d36, createdName=柳叶一刀, createdTime=Mon Feb 01 03:56:59 CST 2021, time=2021-02-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1297510, encodeId=495e129e510bd, content=<a href='/topic/show?id=c0385134ab' target=_blank style='color:#2F92EE;'>#COVID-19患者#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5134, encryptionId=c0385134ab, topicName=COVID-19患者)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6976269, createdName=zhangph, createdTime=Wed Jan 27 12:56:59 CST 2021, time=2021-01-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1541678, encodeId=b14315416e81e, content=<a href='/topic/show?id=fe9c18456c2' target=_blank style='color:#2F92EE;'>#virus#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=18456, encryptionId=fe9c18456c2, topicName=virus)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=823413309323, createdName=sunrural_42825361, createdTime=Wed Jan 27 12:56:59 CST 2021, time=2021-01-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1569780, encodeId=e6881569e8055, content=<a href='/topic/show?id=49e0161680c' target=_blank style='color:#2F92EE;'>#SES#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=16168, encryptionId=49e0161680c, topicName=SES)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=6fc215562628, createdName=dongjia2015, createdTime=Wed Jan 27 12:56:59 CST 2021, time=2021-01-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1029036, encodeId=f024102903662, content=新冠肺炎,疫情何时才能消失, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=公卫新人, createdTime=Tue Jan 26 00:56:59 CST 2021, time=2021-01-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=919880, encodeId=2cc9919880bf, content=凛冬已至,春节欲来。, beContent=null, objectType=article, channel=null, level=null, likeNumber=90, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/Q3auHgzwzM4gCIdSaEkahCNuUWZv4iaKmqvUKHyKnBiarBM9RStQKBeV5Lh6GYYFiamdV5KlSfbLvmAgZTLtq81XA/0, createdBy=13511650672, createdName=言西早, createdTime=Mon Jan 25 22:48:58 CST 2021, time=2021-01-25, status=1, ipAttribution=)]
    2021-01-26 公卫新人

    新冠肺炎,疫情何时才能消失

    0

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    2021-01-25 言西早

    凛冬已至,春节欲来。

    0

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