Department of Microbiology and Immunology, University of Nevada, Reno School of Medicine, Reno, NV, USA.
Kazan Federal University, Kazan, Russian Federation.
Sci Rep. 2017 Nov 22;7(1):16050. doi: 10.1038/s41598-017-16072-3.
ZIKV causes microcephaly by crossing the placental barrier, however, the mechanism of trans-placental dissemination of ZIKV remains unknown. Here, we sought to determine whether monocytes, which can cross tissue barriers, assist ZIKV dissemination to the fetus. We determined this by infecting monocytes with two strains of ZIKV: South American (PRVABC59) and Nigerian (IBH30656) and analyzing viral replication. We found that ZIKV infects and replicates in monocytes and macrophages, which results in the modulation of a large number of cellular genes. Analysis of these genes identified multiple pathways including inflammasome to be targeted by ZIKV, which was confirmed by analyzing the transcript levels of the proteins of inflammasome pathways, NLRP3, ASC, caspase 1, IL-1 and IL-18. Interestingly, IFNα and the IFN inducible gene, MxA were not enhanced, suggesting prevention of innate antiviral defense by ZIKV. Also, inhibition of inflammasome led to an increased transcriptional activity of IFNα, MxA and CXCL10. Based on these results we suggest that ZIKV transcription is regulated by inflammasomes.
寨卡病毒通过胎盘屏障引起小头畸形，但寨卡病毒的跨胎盘传播机制尚不清楚。在这里，我们试图确定是否可以穿过组织屏障的单核细胞有助于寨卡病毒向胎儿的传播。我们通过用两种寨卡病毒株（南美洲（PRVABC59）和尼日利亚（IBH30656））感染单核细胞来确定这一点，并分析病毒复制。我们发现寨卡病毒感染单核细胞和巨噬细胞并在其中复制，这导致大量细胞基因的调节。对这些基因的分析确定了多个途径，包括被寨卡病毒靶向的炎症小体途径，这通过分析炎症小体途径的蛋白质 NLRP3、ASC、半胱天冬酶 1、IL-1 和 IL-18 的转录水平得到证实。有趣的是，IFNα 和 IFN 诱导基因 MxA 没有增强，表明寨卡病毒阻止了先天抗病毒防御。此外，炎症小体的抑制导致 IFNα、MxA 和 CXCL10 的转录活性增加。基于这些结果，我们认为寨卡病毒的转录受到炎症小体的调节。
