小柯机器人

奥地利科学院Jürgen A. Knoblich研究组发现，寨卡病毒和1型单纯疱疹病毒感染的类器官模型揭示导致小头畸形的病毒特异性反应。相关论文于2021年4月9日在线发表在《细胞—干细胞》杂志上。

研究人员使用人脑类器官来研究了由寨卡病毒（ZIKV）和单纯疱疹病毒（HSV-1）引起小头畸形的潜在机制。研究人员发现两种病毒均能在脑类器官中有效复制，并通过引起细胞死亡来减弱其生长。但是，转录谱分析表明ZIKV和HSV-1引发了明显的细胞反应，并且HSV-1独特地损害了神经上皮的身份。

此外，研究人员证明，尽管两种病毒均无法有效诱导I型干扰素系统，但由其感染引起的类器官缺陷可通过独特的I型干扰素得以挽救。这些表型在2D培养中看不到，从而突显了脑类器官在模拟病毒感染中的优越性。这些结果揭示了病毒特有的机制以及与病毒引起小头畸形相关的复杂细胞免疫防御。

据悉，妊娠早期的病毒感染是小头畸形的主要原因。但是，尚不清楚的是，不同的病毒如何损害人的大脑发育。

附：英文原文

Title: Organoid modeling of Zika and herpes simplex virus 1 infections reveals virus-specific responses leading to microcephaly

Author: Veronica Krenn, Camilla Bosone, Thomas R. Burkard, Julia Spanier, Ulrich Kalinke, Arianna Calistri, Cristiano Salata, Raissa Rilo Christoff, Patricia Pestana Garcez, Ali Mirazimi, Jürgen A. Knoblich

Issue&Volume: 2021-04-09

Abstract: Viral infection in early pregnancy is a major cause of microcephaly. However, howdistinct viruses impair human brain development remains poorly understood. Here weuse human brain organoids to study the mechanisms underlying microcephaly caused byZika virus (ZIKV) and herpes simplex virus (HSV-1). We find that both viruses efficientlyreplicate in brain organoids and attenuate their growth by causing cell death. However,transcriptional profiling reveals that ZIKV and HSV-1 elicit distinct cellular responsesand that HSV-1 uniquely impairs neuroepithelial identity. Furthermore, we demonstratethat, although both viruses fail to potently induce the type I interferon system,the organoid defects caused by their infection can be rescued by distinct type I interferons.These phenotypes are not seen in 2D cultures, highlighting the superiority of brainorganoids in modeling viral infections. These results uncover virus-specific mechanismsand complex cellular immune defenses associated with virus-induced microcephaly.

DOI: 10.1016/j.stem.2021.03.004

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(21)00110-7

Cell Stem Cell：《细胞—干细胞》，创刊于2007年。隶属于细胞出版社，最新IF：25.269
官方网址：https://www.cell.com/cell-stem-cell/home
投稿链接：https://www.editorialmanager.com/cell-stem-cell/default.aspx