PMID- 32192194 OWN - NLM STAT- MEDLINE DCOM- 20210217 LR - 20210217 IS - 1999-4915 (Electronic) IS - 1999-4915 (Linking) VI - 12 IP - 3 DP - 2020 Mar 17 TI - Coxsackievirus B3 Infection of Human Neural Progenitor Cells Results in Distinct Expression Patterns of Innate Immune Genes. LID - 10.3390/v12030325 [doi] LID - 325 AB - Coxsackievirus B3 (CVB3), a member of Picornaviridae family, is an important human pathogen that causes a wide range of diseases, including myocarditis, pancreatitis, and meningitis. Although CVB3 has been well demonstrated to target murine neural progenitor cells (NPCs), gene expression profiles of CVB3-infected human NPCs (hNPCs) has not been fully explored. To characterize the molecular signatures and complexity of CVB3-mediated host cellular responses in hNPCs, we performed QuantSeq 3' mRNA sequencing. Increased expression levels of viral RNA sensors (RIG-I, MDA5) and interferon-stimulated genes, such as IFN-beta, IP-10, ISG15, OAS1, OAS2, Mx2, were detected in response to CVB3 infection, while IFN-gamma expression level was significantly downregulated in hNPCs. Consistent with the gene expression profile, CVB3 infection led to enhanced secretion of inflammatory cytokines and chemokines, such as interleukin-6 (IL-6), interleukin-8 (IL-8), and monocyte chemoattractant protein-1 (MCP-1). Furthermore, we show that type I interferon (IFN) treatment in hNPCs leads to significant attenuation of CVB3 RNA copy numbers, whereas, type II IFN (IFN-gamma) treatment enhances CVB3 replication and upregulates suppressor of cytokine signaling 1/3 (SOCS) expression levels. Taken together, our results demonstrate the distinct molecular patterns of cellular responses to CVB3 infection in hNPCs and the pro-viral function of IFN-gamma via the modulation of SOCS expression. FAU - Oh, Soo-Jin AU - Oh SJ AUID- ORCID: 0000-0001-5423-0440 AD - Department of Biomedical Sciences, BK21 PLUS program, College of Medicine, Korea University Guro Hospital, Seoul 08308, Korea. FAU - Gim, Jeong-An AU - Gim JA AD - Medical Science Research Center, College of Medicine, Korea University Guro Hospital, Seoul 08308, Korea. FAU - Lee, Jae Kyung AU - Lee JK AUID- ORCID: 0000-0002-9641-8473 AD - Department of Biomedical Sciences, BK21 PLUS program, College of Medicine, Korea University Guro Hospital, Seoul 08308, Korea. FAU - Park, Hosun AU - Park H AD - Department of Microbiology, College of Medicine, Yeungnam University, 170 Hyeonchung-ro, Namgu, Daegu 42415, Korea. FAU - Shin, Ok Sarah AU - Shin OS AD - Department of Biomedical Sciences, BK21 PLUS program, College of Medicine, Korea University Guro Hospital, Seoul 08308, Korea. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200317 PL - Switzerland TA - Viruses JT - Viruses JID - 101509722 RN - 0 (Cytokines) SB - IM MH - Cell Line MH - Computational Biology/methods MH - Cytokines/metabolism MH - *Disease Susceptibility MH - Enterovirus B, Human/*physiology MH - Enterovirus Infections/genetics/virology MH - Gene Expression Profiling MH - *Gene Expression Regulation MH - *Host-Pathogen Interactions/genetics/immunology MH - Humans MH - Immunity, Innate/*genetics MH - Neural Stem Cells/*metabolism/*virology MH - Signal Transduction MH - Transcriptome PMC - PMC7150933 OTO - NOTNLM OT - Coxsackievirus B3 (CVB3) OT - gene expression profiles OT - interferons OT - neuronal progenitor cells OT - suppressor of cytokine signaling COIS- The authors declare no conflict of interest. EDAT- 2020/03/21 06:00 MHDA- 2021/02/18 06:00 PMCR- 2020/03/01 CRDT- 2020/03/21 06:00 PHST- 2020/02/13 00:00 [received] PHST- 2020/03/09 00:00 [revised] PHST- 2020/03/11 00:00 [accepted] PHST- 2020/03/21 06:00 [entrez] PHST- 2020/03/21 06:00 [pubmed] PHST- 2021/02/18 06:00 [medline] PHST- 2020/03/01 00:00 [pmc-release] AID - v12030325 [pii] AID - viruses-12-00325 [pii] AID - 10.3390/v12030325 [doi] PST - epublish SO - Viruses. 2020 Mar 17;12(3):325. doi: 10.3390/v12030325.