J MICROBIOL METH:30%人类被猫感染弓形虫,通过“精神控制”,让被感染者更爱冒险,CRISPR基因编辑开发出预防疫苗

2020-12-31 生物世界 Bio生物世界

据估计,全世界有超过30%的人类被感染弓形虫,弓形虫感染对免疫力低下者和孕妇有重大威胁。还有研究表明,弓形虫感染会改变宿主行为,让其更渴望探索和冒险。

据估计,全世界有超过30%的人类被感染弓形虫,弓形虫感染对免疫力低下者和孕妇有重大威胁。还有研究表明,弓形虫感染会改变宿主行为,让其更渴望探索和冒险。而一项最新研究则通过CRISPR基因编辑技术构建了弓形虫突变株,能够作为疫苗,阻断猫向人类传播弓形虫。

2012年,韩国上映了一部名为《铁线虫入侵》的生物灾难惊悚电影,电影中,原本寄生于昆虫的铁线虫发生变异而寄生于人体,到达繁殖期的铁线虫会令宿主神志不清,投水自杀,再进入水中大量繁殖。

铁线虫,体型细长,呈马鬃状,最长可达1米,幼虫寄生在螳螂、蝗虫等节肢动物体内,铁线虫幼虫在节肢动物体内会诱使宿主去寻找水源,进而让自己成功进入水中成长并自由生活。铁线虫在世界各地广泛分布,可通过水源感染人体,引起铁线虫病(感染人类的情况比较罕见)。

铁线虫看起来很恐怖,但是好在平时生活中只要注意不接触污水,其实并没有什么机会被感染,而且,人类感染铁线虫的情况很少见。

然而,实际生活中,人类却很容易接触和感染另一种寄生虫——刚地弓形虫。铁线虫会诱使宿主寻找水源,仿佛精神控制一般,而弓形虫对宿主的精神控制有过之而无不及。

多达30%的人类已感染弓形虫

刚地弓形虫(Toxoplasma gondii)是猫科动物的肠道球虫,1908年由法国学者Nicolle及Manceaux在北非刚地梳趾鼠的肝脾单核细胞内发现,虫体呈弓形,命名为刚地弓形虫。

刚地弓形虫在全世界广泛分布,人和许多动物都能感染,随着养猫人群的增加,全世界有近三分之一的人群被感染,中国阳性感染率为5%—20%,部分地区高达30%以上。

刚地弓形虫有一个复杂的生命周期,包括有性和无性两个阶段。尽管这种寄生虫能够感染许多哺乳动物,但它只能在包括家猫在内的猫科动物中完成其生命周期。即,除了终宿主以外,弓形虫在其他动物体内只能进行无性繁殖,不能向外界散播它的后代。

弓形虫感染的潜在危害

刚地弓形虫是一种重要的机会致病原虫(opportunistic protozoan),从上世纪20年代开始,医生开始认识到如果女性在怀孕期间被弓形虫感染,可能会导致婴儿生病,在某些情况下还会导致失明、智力发育迟缓,甚至严重的脑损伤或死亡。

弓形虫也是免疫力低下人群的重大威胁:在艾滋病刚开始流行的时候,科学家还没有研发出有效抗逆转录病毒药物,许多艾滋病患者晚期因弓形虫感染而深受痴呆症折磨。

有些研究认为,弓形虫感染可以潜在地影响人类的行为,甚至世界的文化。例如在2010年南非世界杯淘汰赛阶段的八场比赛中,全部都是弓形虫感染率高的国家获得了胜利。

但好在健康的儿童和成人通常在感染弓形虫初期的症状和普通的流感差不多,只不过在病人抵抗住弓形虫的侵害之后,弓形虫并没有被彻底消灭,还有可能潜伏在大脑细胞中。

弓形虫能够潜伏在大脑,进行精神控制

早期研究发现,弓形虫对啮齿动物(鼠、兔等等)具有一种奇怪的“精神控制”能力,一旦感染了这种大脑寄生虫,小鼠的大脑和行为便受到重大的影响,它们似乎就不再害怕猫,变得更容易被吃掉,这样猫也会更多地感染上弓形虫。

可以说这种寄生虫相当的“聪明”,可以通过“精神控制”操纵被感染者的行为,进而达到繁殖的目的。甚至一些研究将人类感染弓形虫与冲动/精神分裂等心理健康状况联系起来。

但是,弓形虫究竟是如何影响宿主的行为,以及对宿主“精神控制”的能力程度有多高,一直存在着激烈的科学辩论。

2020年1月,瑞士日内瓦大学的研究人员在 Cell 杂志子刊  Cell Reports 杂志发表了题:Neuroinflammation-Associated Aspecific Manipulation of Mouse Predator Fear by Toxoplasma gondii 研究论文。

这项研究表明,刚地弓形虫感染会让老鼠更渴望探索,并消除了对捕食者(不仅仅是对猫)的恐惧,此外,研究发现行为改变的严重程度与大脑中的弓形虫囊肿数量呈正相关,指出了广泛的与免疫相关的行为改变。

这项研究发现:感染弓形虫后的小鼠不仅是不害怕猫,它们心很大,哪哪儿都敢去,冒险精神更强了。但这对小鼠来说,这并不是什么好事,胆大、好奇的小鼠更有可能外出而被吃掉。每当它被吃掉的时候弓形虫都会被传播下去。

那么,为什么感染弓形虫后,小鼠会发生如此巨大的行为改变呢?

研究团队进一步提出,大脑中弓形虫囊肿引起的免疫反应是被感染者行为改变的基础。这项研究发现囊肿在小鼠皮层(大脑外层)的分布大致均匀。对脑组织的遗传分析揭示了某些炎症标志物。研究表明,囊肿的数量和炎症的水平都与被感染小鼠的行为改变程度呈正相关。给感染了弓形虫的小鼠服用消炎药可以逆转它们的一些行为变化。

这项研究结果表明,弓形虫已经找到了一个寄生在大脑中的“绝佳位置”:侵入大脑足以激发一种免疫反应,使宿主向捕食者靠近,但又不足以立即杀死宿主。这可以称得上是“一个非常聪明的策略”。在某种程度上,弓形虫是一个“疯狂的天才”。

CRISPR基因编辑带来解决办法

全世界约有三分之一的人类感染并携带了弓形虫,这些弓形虫给免疫力低下者带来了很大的潜在风险,此外,弓形虫感染对孕妇来说也是一个不能忽视的潜在威胁。因此,预防和控制弓形虫感染,对人类健康和公共卫生有重大意义。

2020年12月,瑞士苏黎世大学的研究人员在 Journal of Biological Methods 杂志发表了题为:A streamlined CRISPR/Cas9 approach for fast genome editing in Toxoplasma gondii and Besnoitia besnoiti 的研究论文。

研究团队通过CRISPR基因编辑技术,创造了一个弓形虫突变株,该突变株表现出受精不良、繁殖力降低,并导致其卵囊无法产生子孢子。用这种基因编辑改造的弓形虫感染猫科动物,能够完全防止弓形虫感染后的卵囊和子孢子的传播。

这表明,这种基因编辑后的弓形虫可作为一种减毒疫苗,能够阻止弓形虫的传播。

更重要的是,研究团队表示,该研究使用电转染Cas9蛋白和化学合成的sgRNA,这种瞬时组分,不含有质粒,在编辑弓形虫基因后,该组分会迅速被降解,能够最大程度避免脱靶效应带来的潜在风险。

弓形虫具有复杂的生命周期,几乎能感染所有的温血动物,包括野生啮齿动物、鸟类、哺乳动物,以及人类。据估计,全世界有超过20亿人感染并携带弓形虫,人类主要通过三种途径感染弓形虫:食源性感染;母婴感染;动物对人感染(主要是宠物猫)。

这项研究中开发的CRISPR基因编辑弓形虫突变株,能够有效预防猫科动物传播弓形虫,从而断绝上述最后一条传播途径。

原始出处:

Adrian B. Hehl, Rahel R. Winiger,et al.A streamlined CRISPR/Cas9 approach for fast genome editing in Toxoplasma gondii and Besnoitia besnoiti. Journal of Biological Methods. DOI: http://dx.doi.org/10.14440/jbm.2020.343

 

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status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1456991, encodeId=e58714569910f, content=<a href='/topic/show?id=4ade4985643' target=_blank style='color:#2F92EE;'>#弓形虫#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=49856, encryptionId=4ade4985643, topicName=弓形虫)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f7095824508, createdName=zhangj7110, createdTime=Sat Jan 02 04:35:27 CST 2021, time=2021-01-02, status=1, ipAttribution=)]
    2021-05-22 sunylz
  3. 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  4. 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  5. 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  6. 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objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11582, encryptionId=4a391158248, topicName=MET)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=18fc139, createdName=一闲, createdTime=Sun Aug 08 18:35:27 CST 2021, time=2021-08-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2084621, encodeId=16cb2084621c7, content=<a href='/topic/show?id=61f411e013b' target=_blank style='color:#2F92EE;'>#Micro#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11701, encryptionId=61f411e013b, topicName=Micro)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d59291, createdName=xjy02, createdTime=Tue Nov 30 18:35:27 CST 2021, time=2021-11-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1276180, encodeId=7fa412e61804f, content=<a href='/topic/show?id=755d5211a0' target=_blank style='color:#2F92EE;'>#CRISPR#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5211, encryptionId=755d5211a0, topicName=CRISPR)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=583c133, createdName=yuandd, createdTime=Sat Jan 02 04:35:27 CST 2021, time=2021-01-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1402603, encodeId=92871402603f8, content=<a href='/topic/show?id=546f9e45197' target=_blank style='color:#2F92EE;'>#防疫#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97451, encryptionId=546f9e45197, topicName=防疫)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=bf7e2418349, createdName=zhangying8789, createdTime=Sat Jan 02 04:35:27 CST 2021, time=2021-01-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1456991, encodeId=e58714569910f, content=<a href='/topic/show?id=4ade4985643' target=_blank style='color:#2F92EE;'>#弓形虫#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=49856, encryptionId=4ade4985643, topicName=弓形虫)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f7095824508, createdName=zhangj7110, createdTime=Sat Jan 02 04:35:27 CST 2021, time=2021-01-02, status=1, ipAttribution=)]
    2021-08-08 一闲
  7. [GetPortalCommentsPageByObjectIdResponse(id=1767816, encodeId=9d031e6781632, content=<a href='/topic/show?id=64f5343e2f' target=_blank style='color:#2F92EE;'>#Biol#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3437, encryptionId=64f5343e2f, topicName=Biol)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8e886, createdName=仁者大医, createdTime=Thu Mar 18 04:35:27 CST 2021, time=2021-03-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1919191, encodeId=b5d0191919115, content=<a href='/topic/show?id=4f26341994' target=_blank style='color:#2F92EE;'>#Bio#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3419, encryptionId=4f26341994, topicName=Bio)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=12de429, 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href='/topic/show?id=755d5211a0' target=_blank style='color:#2F92EE;'>#CRISPR#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5211, encryptionId=755d5211a0, topicName=CRISPR)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=583c133, createdName=yuandd, createdTime=Sat Jan 02 04:35:27 CST 2021, time=2021-01-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1402603, encodeId=92871402603f8, content=<a href='/topic/show?id=546f9e45197' target=_blank style='color:#2F92EE;'>#防疫#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97451, encryptionId=546f9e45197, topicName=防疫)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=bf7e2418349, createdName=zhangying8789, createdTime=Sat Jan 02 04:35:27 CST 2021, time=2021-01-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1456991, encodeId=e58714569910f, content=<a href='/topic/show?id=4ade4985643' target=_blank style='color:#2F92EE;'>#弓形虫#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=49856, encryptionId=4ade4985643, topicName=弓形虫)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f7095824508, createdName=zhangj7110, createdTime=Sat Jan 02 04:35:27 CST 2021, time=2021-01-02, status=1, ipAttribution=)]
    2021-11-30 xjy02
  8. 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href='/topic/show?id=755d5211a0' target=_blank style='color:#2F92EE;'>#CRISPR#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5211, encryptionId=755d5211a0, topicName=CRISPR)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=583c133, createdName=yuandd, createdTime=Sat Jan 02 04:35:27 CST 2021, time=2021-01-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1402603, encodeId=92871402603f8, content=<a href='/topic/show?id=546f9e45197' target=_blank style='color:#2F92EE;'>#防疫#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97451, encryptionId=546f9e45197, topicName=防疫)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=bf7e2418349, createdName=zhangying8789, createdTime=Sat Jan 02 04:35:27 CST 2021, time=2021-01-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1456991, encodeId=e58714569910f, content=<a href='/topic/show?id=4ade4985643' target=_blank style='color:#2F92EE;'>#弓形虫#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=49856, encryptionId=4ade4985643, topicName=弓形虫)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f7095824508, createdName=zhangj7110, createdTime=Sat Jan 02 04:35:27 CST 2021, time=2021-01-02, status=1, ipAttribution=)]
    2021-01-02 yuandd
  9. [GetPortalCommentsPageByObjectIdResponse(id=1767816, encodeId=9d031e6781632, content=<a href='/topic/show?id=64f5343e2f' target=_blank style='color:#2F92EE;'>#Biol#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3437, encryptionId=64f5343e2f, topicName=Biol)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8e886, createdName=仁者大医, createdTime=Thu Mar 18 04:35:27 CST 2021, time=2021-03-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1919191, encodeId=b5d0191919115, content=<a href='/topic/show?id=4f26341994' target=_blank style='color:#2F92EE;'>#Bio#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3419, encryptionId=4f26341994, topicName=Bio)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=12de429, 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status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1456991, encodeId=e58714569910f, content=<a href='/topic/show?id=4ade4985643' target=_blank style='color:#2F92EE;'>#弓形虫#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=49856, encryptionId=4ade4985643, topicName=弓形虫)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f7095824508, createdName=zhangj7110, createdTime=Sat Jan 02 04:35:27 CST 2021, time=2021-01-02, status=1, ipAttribution=)]
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