Nature、Cell同时发布重大成果:动物模型揭开寨卡之谜

2016-05-16 佚名 生物通

寨卡病毒(Zika virus)前段时间在拉美国家造成了严重的疫情。这种病毒感染的症状很像感冒,一般是发烧和肌肉关节疼痛。然而随着疫情愈演愈烈,人们发现寨卡病毒似乎也和新生儿小头畸形有关。目前科学家们还不了解寨卡病毒感染的具体机制,也没有开发出特异性疗法和疫苗。最佳预防方式仍是采取保护措施,避免蚊子叮咬。五月十日,Nature和Cell杂志同时发表了两项寨卡研究的突破性成果。两个相互独立的研究团队

寨卡病毒(Zika virus)前段时间在拉美国家造成了严重的疫情。这种病毒感染的症状很像感冒,一般是发烧和肌肉关节疼痛。然而随着疫情愈演愈烈,人们发现寨卡病毒似乎也和新生儿小头畸形有关。目前科学家们还不了解寨卡病毒感染的具体机制,也没有开发出特异性疗法和疫苗。最佳预防方式仍是采取保护措施,避免蚊子叮咬。

五月十日,Nature和Cell杂志同时发表了两项寨卡研究的突破性成果。两个相互独立的研究团队成功建立了寨卡感染的动物模型,首次直接证实寨卡病毒能够导致严重的出生缺陷。人们可以利用这些动物模型探索巴西寨卡病毒的致病性,开发治疗和预防寨卡感染的有效药物。

加州大学的研究团队在Nature杂志上展现了自己开发的小鼠模型。他们的研究显示,巴西寨卡病毒能够穿越胎盘并感染小鼠胎儿。通过母体感染巴西寨卡病毒的新生小鼠拥有小得不正常的头部,机体生长也更为迟缓。除此之外,这些新生小鼠也出现了其他异常表现,包括眼睛问题和细胞持续死亡。

研究人员指出,小头畸形只是寨卡病毒感染的冰山一角,这种病毒会使子宫内的胎儿生长停滞并且发育不良。媒体用小头畸形来表现寨卡病毒感染只是因为这种图像更有冲击力,这种病毒对人体健康其实有更大的破坏性。值得注意的是,有些个体可能对寨卡病毒感染更加敏感。

研究人员不仅构建了寨卡病毒感染的动物模型,还用人类多能干细胞生成了大脑皮层前体细胞以及大脑类器官。他们发现,巴西寨卡病毒会促使这些前体细胞死亡,抑制大脑类器官的生长,干扰大脑皮层的组织结构。非洲寨卡病毒却没有这么大的影响。可能巴西寨卡病毒发生了某种突变,使其对人类细胞更有侵袭性。

华盛顿大学的研究团队在Cell杂志上发表了自己的寨卡小鼠模型,并在此基础上分析了寨卡病毒的传播路径。研究显示,寨卡病毒能逐步侵入和破坏胎盘,感染小鼠胎儿并引起与人类婴儿类似的症状,最终导致胎儿死亡和其他先天问题。

构建模拟寨卡病毒感染的小鼠模型一直是个大问题,因为小鼠通常对这种病毒并不敏感。为了绕过小鼠的免疫防御,研究妊娠过程中的病毒传播,华盛顿团队开发了两种小鼠模型。一种是经过遗传学改造,免疫系统有缺陷的母鼠。一种是注射免疫抑制性抗体的母鼠。他们在这些小鼠的妊娠过程中观察寨卡病毒感染,发现这种病毒更倾向于感染胎盘,胎盘中的病毒水平比血液中高一千倍。

进一步研究表明,寨卡病毒在妊娠早期跨越母体组织与胎儿之间的屏障。病毒进入胎盘之后会感染滋养层细胞,损伤胎儿毛细血管。许多感染寨卡病毒的小鼠胎儿还未出生就夭折了。侥幸活下来的小鼠体型明显更小,大脑和中枢神经系统都有病毒在复制。

原始出处

Fernanda R. Cugola,Isabella R. Fernandes.et.al The Brazilian Zika virus strain causes birth defects in experimental models.nature.2016

Jonathan J. Miner8, Bin Cao8, Jennifer Govero8.et.al Zika Virus Infection during Pregnancy in Mice Causes Placental Damage and Fetal Demise cell 2016

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    2016-07-27 维他命
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    2017-01-11 智慧医人
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    2016-05-18 吴教授

    希望新的疫苗和根治性药物能早日找到

    0

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