Nascimento Juliana Minardi, Gouvêa-Junqueira Danielle, Zuccoli Giuliana S, Pedrosa Carolina da Silva Gouveia, Brandão-Teles Caroline, Crunfli Fernanda, Antunes André S L M, Cassoli Juliana S, Karmirian Karina, Salerno José Alexandre, de Souza Gabriela Fabiano, Muraro Stéfanie Primon, Proenca-Módena Jose Luiz, Higa Luiza M, Tanuri Amilcar, Garcez Patricia P, Rehen Stevens K, Martins-de-Souza Daniel
Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Rua Monteiro Lobato, Campinas, SP, 255, 13083-862, Brazil.
D'Or Institute for Research and Education (IDOR), Rua Diniz Cordeiro, 30, Rio de Janeiro, RJ, 22281-100, Brazil.
Mol Neurobiol. 2022 Sep;59(9):5549-5563. doi: 10.1007/s12035-022-02922-3. Epub 2022 Jun 22.
Brain abnormalities and congenital malformations have been linked to the circulating strain of Zika virus (ZIKV) in Brazil since 2016 during the microcephaly outbreak; however, the molecular mechanisms behind several of these alterations and differential viral molecular targets have not been fully elucidated. Here we explore the proteomic alterations induced by ZIKV by comparing the Brazilian (Br ZIKV) and the African (MR766) viral strains, in addition to comparing them to the molecular responses to the Dengue virus type 2 (DENV). Neural stem cells (NSCs) derived from induced pluripotent stem (iPSCs) were cultured both as monolayers and in suspension (resulting in neurospheres), which were then infected with ZIKV (Br ZIKV or ZIKV MR766) or DENV to assess alterations within neural cells. Large-scale proteomic analyses allowed the comparison not only between viral strains but also regarding the two- and three-dimensional cellular models of neural cells derived from iPSCs, and the effects on their interaction. Altered pathways and biological processes were observed related to cell death, cell cycle dysregulation, and neurogenesis. These results reinforce already published data and provide further information regarding the biological alterations induced by ZIKV and DENV in neural cells.
自2016年巴西小头畸形疫情爆发以来，脑部异常和先天性畸形就与寨卡病毒（ZIKV）的流行毒株有关；然而，这些改变背后的分子机制以及不同的病毒分子靶点尚未完全阐明。在这里，我们通过比较巴西（Br ZIKV）和非洲（MR766）病毒株，以及将它们与对2型登革热病毒（DENV）的分子反应进行比较，来探索ZIKV诱导的蛋白质组学改变。源自诱导多能干细胞（iPSC）的神经干细胞（NSC）既可以单层培养，也可以悬浮培养（形成神经球），然后用ZIKV（Br ZIKV或ZIKV MR766）或DENV感染，以评估神经细胞内的变化。大规模蛋白质组学分析不仅可以比较病毒株，还可以比较源自iPSC的神经细胞的二维和三维细胞模型，以及对它们相互作用的影响。观察到与细胞死亡、细胞周期失调和神经发生相关的改变途径和生物学过程。这些结果强化了已发表的数据，并提供了有关ZIKV和DENV在神经细胞中诱导的生物学改变的进一步信息。
