Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
National Institute of Science and Technology on Neuroimmunomodulation (INCT-NIM); Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
Sci Rep. 2020 Jan 28;10(1):1378. doi: 10.1038/s41598-020-58135-y.
Previous work showed that the thymus can be infected by RNA viruses as HIV and HTLV-1. We thus hypothesized that the thymus might also be infected by the Zika virus (ZIKV). Herein we provide compelling evidence that ZIKV targets human thymic epithelial cells (TEC) in vivo and in vitro. ZIKV-infection enhances keratinization of TEC, with a decrease in proliferation and increase in cell death. Moreover, ZIKV modulates a high amount of coding RNAs with upregulation of genes related to cell adhesion and migration, as well as non-coding genes including miRNAs, circRNAs and lncRNAs. Moreover, we observed enhanced attachment of lymphoblastic T-cells to infected TEC, as well as virus transfer to those cells. Lastly, alterations in thymuses from babies congenitally infected were seen, with the presence of viral envelope protein in TEC. Taken together, our data reveals that the thymus, particularly the thymic epithelium, is a target for the ZIKV with changes in the expression of molecules that are relevant for interactions with developing thymocytes.
先前的研究表明,胸腺可能会被 HIV 和 HTLV-1 等 RNA 病毒感染。因此,我们假设,胸腺也可能会受到寨卡病毒(ZIKV)的感染。在此,我们提供了确凿的证据表明,ZIKV 可在体内和体外靶向人胸腺上皮细胞(TEC)。ZIKV 感染会增强 TEC 的角化,导致增殖减少和细胞死亡增加。此外,ZIKV 还会调节大量的编码 RNA,上调与细胞黏附和迁移相关的基因,以及非编码基因,包括 miRNA、circRNA 和 lncRNA。此外,我们观察到感染的 TEC 对淋巴母细胞 T 细胞的附着增强,以及病毒向这些细胞的转移。最后,我们还发现先天性感染 ZIKV 的婴儿的胸腺发生了改变,TEC 中存在病毒包膜蛋白。综上所述,我们的数据表明,胸腺,特别是胸腺上皮,是 ZIKV 的靶标,其与发育中的胸腺细胞相互作用的相关分子的表达发生了改变。