PMID- 32902370 OWN - NLM STAT- MEDLINE DCOM- 20210609 LR - 20210609 IS - 2222-1751 (Electronic) IS - 2222-1751 (Linking) VI - 9 IP - 1 DP - 2020 Dec TI - mRNA and miRNA profiling of Zika virus-infected human umbilical cord mesenchymal stem cells identifies miR-142-5p as an antiviral factor. PG - 2061-2075 LID - 10.1080/22221751.2020.1821581 [doi] AB - 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. FAU - Seong, Rak-Kyun AU - Seong RK AD - Department of Biomedical Sciences, College of Medicine, Korea University Guro Hospital, Seoul, Republic of Korea. FAU - Lee, Jae Kyung AU - Lee JK AD - Department of Biomedical Sciences, College of Medicine, Korea University Guro Hospital, Seoul, Republic of Korea. FAU - Cho, Geum Joon AU - Cho GJ AD - Department of Obstetrics and Gynaecology, College of Medicine, Korea University Guro Hospital, Seoul, Republic of Korea. FAU - Kumar, Mukesh AU - Kumar M AUID- ORCID: 0000-0003-0970-4875 AD - Department of Biology, Georgia State University, Atlanta, Georgia, USA. FAU - Shin, Ok Sarah AU - Shin OS AD - Department of Biomedical Sciences, College of Medicine, Korea University Guro Hospital, Seoul, Republic of Korea. LA - eng GR - R21 NS099838/NS/NINDS NIH HHS/United States GR - R21 OD024896/OD/NIH HHS/United States PT - Journal Article PL - United States TA - Emerg Microbes Infect JT - Emerging microbes & infections JID - 101594885 RN - 0 (Antiviral Agents) RN - 0 (MIRN142 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (RNA, Messenger) SB - IM MH - A549 Cells MH - Animals MH - Antiviral Agents/immunology MH - Cell Line MH - Cells, Cultured MH - Chlorocebus aethiops MH - *Gene Expression Profiling MH - Gene Expression Regulation MH - HeLa Cells MH - Host Microbial Interactions MH - Humans MH - Immunity, Innate MH - Mesenchymal Stem Cells/virology MH - MicroRNAs/*genetics MH - Mitochondria/*metabolism/virology MH - RNA, Messenger/*genetics MH - Sequence Analysis, RNA MH - Signal Transduction MH - Umbilical Cord/virology MH - Vero Cells MH - Virus Attachment MH - Virus Internalization MH - Virus Replication MH - Zika Virus MH - Zika Virus Infection/*genetics/immunology PMC - PMC7534337 OTO - NOTNLM OT - RNA-seq OT - ZIKV OT - hUCMSCs OT - innate immunity OT - miRNA OT - small RNA-seq COIS- No potential conflict of interest was reported by the author(s). EDAT- 2020/09/10 06:00 MHDA- 2021/06/10 06:00 PMCR- 2020/09/22 CRDT- 2020/09/09 12:23 PHST- 2020/09/10 06:00 [pubmed] PHST- 2021/06/10 06:00 [medline] PHST- 2020/09/09 12:23 [entrez] PHST- 2020/09/22 00:00 [pmc-release] AID - 1821581 [pii] AID - 10.1080/22221751.2020.1821581 [doi] PST - ppublish SO - Emerg Microbes Infect. 2020 Dec;9(1):2061-2075. doi: 10.1080/22221751.2020.1821581.