西班牙巴塞罗那分子生物学研究所（IBMB-CSIC）Elisa Martí和Murielle Saade团队合作取得最新进展。他们发现寨卡病毒（ZikV）-NS5的多聚化导致纤毛病并迫使过早神经发生。相关论文于2020年11月3日发表在《细胞-干细胞》杂志上。

他们显示ZikV-NS5蛋白与神经祖细胞中初级纤毛基底处的宿主蛋白相互作用，导致非典型非遗传性纤毛病和神经元过早分层。此外，在人的微头状胎儿脑组织中，ZikV-NS5持续存在于室管膜细胞的运动性纤毛的基部，其也表现出严重的纤毛病。尽管ZikV-NS5的酶活性似乎是必需的，但参与NS5低聚的氨基酸Y25、K28和K29对于定植和与纤毛碱基成分相互作用，促进纤毛病和过早的神经发生是必不可少的。这些发现为靶向ZikV-NS5多聚化并预防与先天性Zika综合征相关的发育畸形疗法奠定了基础。

研究表明，ZikV是一种黄病毒，可感染神经组织，引起先天性小头畸形。尽管尚不清楚所涉及的潜在细胞事件，ZikV已经进化出多种机制来限制增殖并增加细胞死亡。

附：英文原文

Title: Multimerization of Zika Virus-NS5 Causes Ciliopathy and Forces Premature Neurogenesis

Author: Murielle Saade, Diego S. Ferrero, José Blanco-Ameijeiras, Elena Gonzalez-Gobartt, Marco Flores-Mendez, Victor M. Ruiz-Arroyo, Elena Martínez-Sáez, Santiago Ramón y Cajal, Naiara Akizu, Nuria Verdaguer, Elisa Martí

Issue&Volume: 2020-11-03

Abstract: Zika virus (ZikV) is a flavivirus that infects neural tissues, causing congenitalmicrocephaly. ZikV has evolved multiple mechanisms to restrict proliferation and enhancecell death, although the underlying cellular events involved remain unclear. Herewe show that the ZikV-NS5 protein interacts with host proteins at the base of theprimary cilia in neural progenitor cells, causing an atypical non-genetic ciliopathyand premature neuron delamination. Furthermore, in human microcephalic fetal braintissue, ZikV-NS5 persists at the base of the motile cilia in ependymal cells, whichalso exhibit a severe ciliopathy. Although the enzymatic activity of ZikV-NS5 appearsto be dispensable, the amino acids Y25, K28, and K29 that are involved in NS5 oligomerizationare essential for localization and interaction with components of the cilium base,promoting ciliopathy and premature neurogenesis. These findings lay the foundationfor therapies that target ZikV-NS5 multimerization and prevent the developmental malformationsassociated with congenital Zika syndrome.

DOI: 10.1016/j.stem.2020.10.002

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(20)30496-3