title: Differential Responses of Human Fetal Brain Neural Stem Cells to Zika Virus Infection.
abstract: Zika virus (ZIKV) infection causes microcephaly in a subset of infants born to infected pregnant mothers. It is unknown whether human individual differences contribute to differential susceptibility of ZIKV-related neuropathology. Here, we use an Asian-lineage ZIKV strain, isolated from the 2015 Mexican outbreak (Mex1-7), to infect primary human neural stem cells (hNSCs) originally derived from three individual fetal brains. All three strains of hNSCs exhibited similar rates of Mex1-7 infection and reduced proliferation. However, Mex1-7 decreased neuronal differentiation in only two of the three stem cell strains. Correspondingly, ZIKA-mediated transcriptome alterations were similar in these two strains but significantly different from that of the third strain with no ZIKV-induced neuronal reduction. This study thus confirms that an Asian-lineage ZIKV strain infects primary hNSCs and demonstrates a cell-strain-dependent response of hNSCs to ZIKV infection.
authors.affiliation: Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Erica L
authors.initials: EL
authors.lastname: McGrath
authors.affiliation: Department of Pathology, Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, TX 77555, USA; Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Shannan L
authors.initials: SL
authors.lastname: Rossi
authors.affiliation: Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Junling
authors.initials: J
authors.lastname: Gao
authors.affiliation: Sealy Center for Molecular Medicine, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Widen
authors.affiliation: Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Auston C
authors.initials: AC
authors.lastname: Grant
authors.affiliation: Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Tiffany J
authors.initials: TJ
authors.lastname: Dunn
authors.affiliation: Department of Pathology, Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, TX 77555, USA; Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX 77555, USA; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Sasha R
authors.initials: SR
authors.lastname: Azar
authors.affiliation: Department of Pathology, Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, TX 77555, USA; Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX 77555, USA; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Roundy
authors.affiliation: Department of Radiology and Oncology, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xiong
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Prusak
authors.affiliation: Department of Radiology and Oncology, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Bradford D
authors.initials: BD
authors.lastname: Loucas
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Wood
authors.affiliation: Department of Radiology and Oncology, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Yongjia
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Instituto Nacional de Salud Pública, Centro Regional de Salud Pública, Tapachula, Chiapas 30700, Mexico.
authors.forename: Ildefonso
authors.initials: I
authors.lastname: Fernández-Salas
authors.affiliation: Department of Pathology, Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, TX 77555, USA; Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX 77555, USA; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Scott C
authors.initials: SC
authors.lastname: Weaver
authors.affiliation: Department of Pathology, Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, TX 77555, USA; Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX 77555, USA. Electronic address: nivasila@utmb.edu.
authors.forename: Nikos
authors.initials: N
authors.lastname: Vasilakis
authors.affiliation: Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX 77555, USA; Beijing Institute for Brain Disorders, Capital Medical University, Beijing 100069, China. Electronic address: piwu@utmb.edu.
authors.forename: Ping
authors.initials: P
authors.lastname: Wu
mesh_terms: D000818:Animals; D001253:Astrocytes; D001921:Brain / Q000276:immunology / Q000378:metabolism* / Q000821:virology*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D002522:Chlorocebus aethiops; D016000:Cluster Analysis; D005333:Fetus; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D007113:Immunity, Innate; D008297:Male; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism* / Q000821:virology*; D055495:Neurogenesis / Q000235:genetics; D009474:Neurons; D059467:Transcriptome; D014709:Vero Cells; D000071244:Zika Virus / Q000145:classification / Q000502:physiology*; D000071243:Zika Virus Infection / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000821:virology*
keywords: Zika virus; astrocyte; differentiation; human neural stem cell; innate immunity; neurogenesis; neuron; proliferation; transcriptome