Zika virus (ZIKV) infection during pregnancy is associated with congenital brain abnormalities, a finding that highlights the urgent need to understand mother-to-fetus transmission mechanisms. Human umbilical cord mesenchymal stem cells (hUCMSCs) are susceptible to ZIKV infection but the underlying mechanisms of viral susceptibility remain largely unexplored. In this study, we have characterized and compared host mRNA and miRNA expression profiles in hUCMSCs after infection with two lineages of ZIKV, African (MR766) and Asian (PRVABC59). RNA sequencing analysis identified differentially expressed genes involved in anti-viral immunity and mitochondrial dynamics following ZIKV infection. In particular, ZIKV-infected hUCMSCs displayed mitochondrial elongation and the treatment of hUCMSCs with mitochondrial fission inhibitor led to a dose-dependent increase in ZIKV gene expression and decrease in anti-viral signalling pathways. Moreover, small RNA sequencing analysis identified several significantly up- or down-regulated microRNAs. Interestingly, miR-142-5p was significantly downregulated upon ZIKV infection, whereas cellular targets of miR-142-5p, IL6ST and ITGAV, were upregulated. Overexpression of miR-142-5p resulted in the suppression of ZIKV replication. Furthermore, blocking ITGAV expression resulted in a significant suppression of ZIKV binding to cells, suggesting a potential role of ITGAV in ZIKV entry. In conclusion, these results demonstrate both common and specific host responses to African and Asian ZIKV lineages and indicate miR-142-5p as a key regulator of ZIKV replication in the umbilical cords.
Bibliographical noteFunding Information:
This research was supported by the Basic Science Research Programme of the National Research Foundation of Korea (NRF) and the Ministry of Science, ICT & Future Planning [grant number NRF-2019R1A2C1005961] and Korea University Future Research Grant. M.K. is supported by a National Institute of Neurological Disorders and Stroke [grant number R21NS099838] and Office of the Director, National Institute of Health [grant number R21OD024896]. We thank Dr. Jeong-An Gim (Korea University Guro Hospital) for help with small RNA sequencing analysis.
© 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group, on behalf of Shanghai Shangyixun Cultural Communication Co., Ltd.
- innate immunity
- small RNA-seq
ASJC Scopus subject areas
- Drug Discovery
- Infectious Diseases