Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
Laboratório de Pesquisa Clínica e Translacional (LPCT), Instituto Gonçalo Moniz, Salvador, Brazil.
PLoS One. 2024 Mar 21;19(3):e0290209. doi: 10.1371/journal.pone.0290209. eCollection 2024.
Zika virus (ZIKV) outbreak caused one of the most significant medical emergencies in the Americas due to associated microcephaly in newborns. To evaluate the impact of ZIKV infection on neuronal cells over time, we retrieved gene expression data from several ZIKV-infected samples obtained at different time point post-infection (pi). Differential gene expression analysis was applied at each time point, with more differentially expressed genes (DEG) identified at 72h pi. There were 5 DEGs (PLA2G2F, TMEM71, PKD1L2, UBD, and TNFAIP3 genes) across all timepoints, which clearly distinguished between infected and healthy samples. The highest expression levels of all five genes were identified at 72h pi. Taken together, our results indicate that ZIKV infection greatly impacts human neural cells at early times of infection, with peak perturbation observed at 72h pi. Our analysis revealed that all five DEGs, in samples of ZIKV-infected human neural stem cells, remained highly upregulated across the timepoints evaluated. Moreover, despite the pronounced inflammatory host response observed throughout infection, the impact of ZIKV is variable over time. Finally, the five DEGs identified herein play prominent roles in infection, and could serve to guide future investigations into virus-host interaction, as well as constitute targets for therapeutic drug development.
寨卡病毒(ZIKV)爆发是美洲发生的最重大的医学紧急事件之一,原因是与新生儿小头畸形有关。为了评估寨卡病毒感染对神经元细胞随时间推移的影响,我们从感染后不同时间点获得的多个寨卡病毒感染样本中检索了基因表达数据。在每个时间点都进行了差异基因表达分析,在 72 小时 pi 时鉴定出更多差异表达基因(DEG)。在所有时间点都有 5 个 DEG(PLA2G2F、TMEM71、PKD1L2、UBD 和 TNFAIP3 基因),这些基因可明确区分感染和健康样本。所有五个基因的最高表达水平都在 72 小时 pi 时被鉴定出来。综上所述,我们的结果表明寨卡病毒感染在感染早期对人类神经细胞有很大影响,在 72 小时 pi 时观察到最大的干扰。我们的分析表明,在感染的人类神经干细胞样本中,所有五个 DEG 在评估的所有时间点都保持高度上调。此外,尽管在整个感染过程中观察到明显的炎症宿主反应,但寨卡病毒的影响随时间而变化。最后,本文鉴定的五个 DEG 在感染中起重要作用,可以指导未来对病毒-宿主相互作用的研究,并构成治疗药物开发的目标。