Functional and gene expression profiles to provide clues to the mechanisms involved in susceptibility or resistance of skeletal muscle cells to ZIKV infection

The Zika virus (ZIKV) is an arthropod-borne virus (arbovirus) and belongs to the Flaviviridae family. The main manifestation of the Congenital Zika syndrome is the severe malformation of the central nervous system as well as congenital contractures such as arthrogryposis. Neuromuscular comorbidities are highly prevalent in children that have been congenitally infected by the ZIKV. Microcephaly and arthrogryposis occur during the fetal phase and infancy, when myoblasts are continually merging into myotubes to promote muscle growth. It has been demonstrated that human primary myoblasts can be infected by ZIKV in vitro, whereas myotubes are rather resistant to infection, suggesting that muscle cells can account for a peripheral site of viral amplification, which in turn, may contribute to the pathophysiology of Zika infection. In this study we aim to analyze functional and gene expression profiles to provide clues to the mechanisms involved in susceptibility or resistance of skeletal muscle cells to ZIKV infection.

寨卡病毒（Zika virus, ZIKV）属于黄病毒科（Flaviviridae），是一种节肢动物传播病毒（arbovirus，虫媒病毒）。先天性寨卡综合征的主要临床表现为中枢神经系统严重畸形，以及以关节弯曲症（arthrogryposis）为代表的先天性挛缩。先天性感染寨卡病毒的儿童群体中，神经肌肉合并症极为高发。小头畸形与关节弯曲症可出现于胎儿期及婴儿期——此阶段成肌细胞（myoblasts）持续融合为肌管（myotubes）以促进肌肉生长。已有研究证实，人原代成肌细胞可在体外（in vitro）被寨卡病毒感染，而肌管则对感染具有显著抵抗力，这提示骨骼肌细胞可作为病毒扩增的外周位点，进而可能参与寨卡病毒感染的病理生理进程。本研究旨在分析骨骼肌细胞对寨卡病毒感染的易感性与抵抗性相关的功能及基因表达谱，为阐明其潜在作用机制提供线索。