{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T16:29:01Z","timestamp":1769099341980,"version":"3.49.0"},"update-to":[{"DOI":"10.1371\/journal.pntd.0009183","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,3,15]],"date-time":"2021-03-15T00:00:00Z","timestamp":1615766400000}}],"reference-count":77,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2021,3,3]],"date-time":"2021-03-03T00:00:00Z","timestamp":1614729600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21AI129509-01"],"award-info":[{"award-number":["R21AI129509-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI120942"],"award-info":[{"award-number":["AI120942"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI142759"],"award-info":[{"award-number":["AI142759"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI127744"],"award-info":[{"award-number":["AI127744"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI136126"],"award-info":[{"award-number":["AI136126"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"UTMB CRO Special Fund"},{"DOI":"10.13039\/100006988","name":"John S. Dunn Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100006988","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100006988","name":"John S. Dunn Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100006988","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100006988","name":"John S. Dunn Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100006988","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100012394","name":"Kleberg Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100012394","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100001023","name":"Amon G. Carter Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001023","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Summerfield Robert Foundation"},{"DOI":"10.13039\/100010470","name":"Gillson Longenbaugh Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010470","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI078878"],"award-info":[{"award-number":["AI078878"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI078878"],"award-info":[{"award-number":["AI078878"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"McLaughlin Fellowship"}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:p>Global Zika virus (ZIKV) outbreaks and their strong link to microcephaly have raised major public health concerns. ZIKV has been reported to affect the innate immune responses in neural stem\/progenitor cells (NS\/PCs). However, it is unclear how these immune factors affect neurogenesis. In this study, we used Asian-American lineage ZIKV strain PRVABC59 to infect primary human NS\/PCs originally derived from fetal brains. We found that ZIKV overactivated key molecules in the innate immune pathways to impair neurogenesis in a cell stage-dependent manner. Inhibiting the overactivated innate immune responses ameliorated ZIKV-induced neurogenesis reduction. This study thus suggests that orchestrating the host innate immune responses in NS\/PCs after ZIKV infection could be promising therapeutic approach to attenuate ZIKV-associated neuropathology.<\/jats:p>","DOI":"10.1371\/journal.pntd.0009183","type":"journal-article","created":{"date-parts":[[2021,3,3]],"date-time":"2021-03-03T19:43:12Z","timestamp":1614800592000},"page":"e0009183","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":11,"title":["Inhibition of innate immune response ameliorates Zika virus-induced neurogenesis deficit in human neural stem cells"],"prefix":"10.1371","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9480-8021","authenticated-orcid":true,"given":"Pei","family":"Xu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junling","family":"Gao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3953-3782","authenticated-orcid":true,"given":"Chao","family":"Shan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiffany J.","family":"Dunn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0918-016X","authenticated-orcid":true,"given":"Xuping","family":"Xie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2520-7038","authenticated-orcid":true,"given":"Hongjie","family":"Xia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Zou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beatriz H.","family":"Thames","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amulya","family":"Sajja","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6007-8596","authenticated-orcid":true,"given":"Yongjia","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8413-8960","authenticated-orcid":true,"given":"Alexander N.","family":"Freiberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0708-3289","authenticated-orcid":true,"given":"Nikos","family":"Vasilakis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pei-Yong","family":"Shi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8016-8556","authenticated-orcid":true,"given":"Scott C.","family":"Weaver","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7020-6237","authenticated-orcid":true,"given":"Ping","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2021,3,3]]},"reference":[{"issue":"8","key":"pntd.0009183.ref001","article-title":"Microcephaly Prevalence in Infants Born to Zika Virus-Infected Women: A Systematic Review and Meta-Analysis","volume":"18","author":"AVC Coelho","year":"2017","journal-title":"Int J Mol Sci"},{"issue":"24","key":"pntd.0009183.ref002","doi-asserted-by":"crossref","first-page":"2321","DOI":"10.1056\/NEJMoa1602412","article-title":"Zika Virus Infection in Pregnant Women in Rio de Janeiro","volume":"375","author":"P Brasil","year":"2016","journal-title":"N Engl J Med"},{"issue":"23","key":"pntd.0009183.ref003","doi-asserted-by":"crossref","first-page":"615","DOI":"10.15585\/mmwr.mm6623e1","article-title":"Pregnancy Outcomes After Maternal Zika Virus Infection During Pregnancy\u2014U.S. Territories, January 1, 2016-April 25, 2017","volume":"66","author":"CK Shapiro-Mendoza","year":"2017","journal-title":"MMWR Morb Mortal Wkly Rep"},{"issue":"13","key":"pntd.0009183.ref004","doi-asserted-by":"crossref","first-page":"366","DOI":"10.15585\/mmwr.mm6613e1","article-title":"Vital Signs: Update on Zika Virus-Associated Birth Defects and Evaluation of All U.S. Infants with Congenital Zika Virus Exposure\u2014U.S. Zika Pregnancy Registry, 2016","volume":"66","author":"MR Reynolds","year":"2017","journal-title":"MMWR Morb Mortal Wkly Rep"},{"issue":"9","key":"pntd.0009183.ref005","doi-asserted-by":"crossref","first-page":"242","DOI":"10.15585\/mmwr.mm6509e2","article-title":"Increase in Reported Prevalence of Microcephaly in Infants Born to Women Living in Areas with Confirmed Zika Virus Transmission During the First Trimester of Pregnancy\u2014Brazil, 2015","volume":"65","author":"W Kleber de Oliveira","year":"2016","journal-title":"MMWR Morb Mortal Wkly Rep"},{"issue":"5","key":"pntd.0009183.ref006","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1016\/j.cell.2016.05.008","article-title":"Zika Virus Infection during Pregnancy in Mice Causes Placental Damage and Fetal Demise","volume":"165","author":"JJ Miner","year":"2016","journal-title":"Cell"},{"issue":"3","key":"pntd.0009183.ref007","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1016\/j.chom.2017.08.012","article-title":"Gestational Stage and IFN-\u03bb Signaling Regulate ZIKV Infection In Utero","volume":"22","author":"BW Jagger","year":"2017","journal-title":"Cell Host Microbe"},{"issue":"6","key":"pntd.0009183.ref008","doi-asserted-by":"crossref","first-page":"1588","DOI":"10.1016\/j.celrep.2017.10.059","article-title":"Outcomes of Congenital Zika Disease Depend on Timing of Infection and Maternal-Fetal Interferon Action","volume":"21","author":"J Chen","year":"2017","journal-title":"Cell Rep"},{"issue":"4","key":"pntd.0009183.ref009","doi-asserted-by":"crossref","first-page":"403.e1","DOI":"10.1016\/j.ajog.2018.06.005","article-title":"Timing of gestational exposure to Zika virus is associated with postnatal growth restriction in a murine model","volume":"219","author":"GC Valentine","year":"2018","journal-title":"Am J Obstet Gynecol"},{"issue":"5","key":"pntd.0009183.ref010","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1016\/j.cell.2016.08.004","article-title":"Vaginal Exposure to Zika Virus during Pregnancy Leads to Fetal Brain Infection","volume":"166","author":"LJ Yockey","year":"2016","journal-title":"Cell"},{"issue":"7","key":"pntd.0009183.ref011","article-title":"Role of microglia in the dissemination of Zika virus from mother to fetal brain","volume":"14","year":"2020","journal-title":"PLoS neglected tropical diseases"},{"issue":"5","key":"pntd.0009183.ref012","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1016\/j.stem.2016.02.016","article-title":"Zika Virus Infects Human Cortical Neural Progenitors and Attenuates Their Growth","volume":"18","author":"H Tang","year":"2016","journal-title":"Cell Stem Cell"},{"issue":"1","key":"pntd.0009183.ref013","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.stem.2016.04.017","article-title":"Zika Virus Disrupts Neural Progenitor Development and Leads to Microcephaly in Mice","volume":"19","author":"C Li","year":"2016","journal-title":"Cell Stem Cell"},{"issue":"6287","key":"pntd.0009183.ref014","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1126\/science.aaf6116","article-title":"Zika virus impairs growth in human neurospheres and brain organoids","volume":"352","author":"PP Garcez","year":"2016","journal-title":"Science"},{"issue":"3","key":"pntd.0009183.ref015","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1016\/j.stemcr.2017.01.008","article-title":"Differential Responses of Human Fetal Brain Neural Stem Cells to Zika Virus Infection","volume":"8","author":"EL McGrath","year":"2017","journal-title":"Stem Cell Reports"},{"issue":"6346","key":"pntd.0009183.ref016","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1126\/science.aam9243","article-title":"Neurodevelopmental protein Musashi 1 interacts with the Zika genome and promotes viral replication","volume":"357","author":"PL Chavali","year":"2017","journal-title":"Science"},{"issue":"2","key":"pntd.0009183.ref017","article-title":"Mouse-Musashi-1, a Neural RNA-binding Protein Highly Enriched in the Mammalian CNS Stem Cell","volume":"176","author":"S S","year":"1996","journal-title":"Developmental biology"},{"key":"pntd.0009183.ref018","first-page":"3888","article-title":"The Neural RNA-Binding Protein Musashi1 Translationally Regulates Mammalian numb Gene Expression by Interacting with Its mRNA","author":"T Imai","journal-title":"Mol Cell Biol"},{"issue":"1","key":"pntd.0009183.ref019","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1080\/22221751.2019.1637283","article-title":"Zika virus differentially infects human neural progenitor cells according to their state of differentiation and dysregulates neurogenesis through the Notch pathway","volume":"8","author":"P Ferraris","year":"2019","journal-title":"Emerg Microbes Infect"},{"issue":"6","key":"pntd.0009183.ref020","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1016\/j.jmb.2013.11.024","article-title":"Toll-like receptors in antiviral innate immunity","volume":"426","author":"SN Lester","year":"2014","journal-title":"J Mol Biol"},{"issue":"1","key":"pntd.0009183.ref021","article-title":"Sensing of Viral Infection and Activation of Innate Immunity by Toll-Like Receptor 3","volume":"21","author":"V E","year":"2008","journal-title":"Clinical microbiology reviews"},{"key":"pntd.0009183.ref022","author":"S Uematsu","year":"2007","journal-title":"Toll-like Receptors and Type I Interferons"},{"key":"pntd.0009183.ref023","author":"H Negishi","year":"2008","journal-title":"A critical link between Toll-like receptor 3 and type II interferon signaling pathways in antiviral innate immunity"},{"key":"pntd.0009183.ref024","author":"I Ioannidis","year":"2013","journal-title":"Toll-Like Receptor Expression and Induction of Type I and Type III Interferons in Primary Airway Epithelial Cells"},{"issue":"51","key":"pntd.0009183.ref025","doi-asserted-by":"crossref","first-page":"13978","DOI":"10.1523\/JNEUROSCI.2140-08.2008","article-title":"Toll-like receptor 3 is a negative regulator of embryonic neural progenitor cell proliferation","volume":"28","author":"JD Lathia","year":"2008","journal-title":"J Neurosci"},{"issue":"2","key":"pntd.0009183.ref026","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.stem.2016.04.014","article-title":"Zika Virus Depletes Neural Progenitors in Human Cerebral Organoids through Activation of the Innate Immune Receptor TLR3","volume":"19","author":"J Dang","year":"2016","journal-title":"Cell Stem Cell"},{"issue":"12","key":"pntd.0009183.ref027","doi-asserted-by":"crossref","first-page":"2607","DOI":"10.1038\/s41418-019-0324-7","article-title":"Protection of ZIKV infection-induced neuropathy by abrogation of acute antiviral response in human neural progenitors","volume":"26","author":"L Liu","year":"2019","journal-title":"Cell Death & Differentiation"},{"key":"pntd.0009183.ref028","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.ebiom.2017.02.003","article-title":"A cDNA Clone-Launched Platform for High-Yield Production of Inactivated Zika Vaccine","volume":"17","author":"Y Yang","year":"2017","journal-title":"EBioMedicine"},{"issue":"5","key":"pntd.0009183.ref029","article-title":"Effect of Growth Factors on Proliferation and Phenotypic Differentiation of Human Fetal Neural Stem Cells","volume":"78","author":"T YI","year":"2004","journal-title":"Journal of neuroscience research"},{"issue":"12","key":"pntd.0009183.ref030","article-title":"Region-specific Generation of Cholinergic Neurons From Fetal Human Neural Stem Cells Grafted in Adult Rat","volume":"5","author":"W P","year":"2002","journal-title":"Nature neuroscience"},{"key":"pntd.0009183.ref031","article-title":"Zika Virus Infection of Cultured Human Fetal Brain Neural Stem Cells for Immunocytochemical Analysis","author":"EL McGrath","year":"2018","journal-title":"J Vis Exp"},{"issue":"1","key":"pntd.0009183.ref032","article-title":"Human neural stem cell-derived neuron\/astrocyte co-cultures respond to La Crosse virus infection with proinflammatory cytokines and chemokines","volume":"15","author":"D BE","year":"2018","journal-title":"Journal of neuroinflammation"},{"issue":"6","key":"pntd.0009183.ref033","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1016\/j.chom.2016.05.004","article-title":"An Infectious cDNA Clone of Zika Virus to Study Viral Virulence, Mosquito Transmission, and Antiviral Inhibitors","volume":"19","author":"C Shan","year":"2016","journal-title":"Cell Host Microbe"},{"key":"pntd.0009183.ref034","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.ijid.2017.07.017","article-title":"Zika virus epidemic in Puerto Rico: Health justice too long delayed","volume":"65","author":"CE Rodr\u00edguez-D\u00edaz","year":"2017","journal-title":"Int J Infect Dis"},{"issue":"10","key":"pntd.0009183.ref035","doi-asserted-by":"crossref","DOI":"10.3390\/v10100550","article-title":"Strain-Dependent Consequences of Zika Virus Infection and Differential Impact on Neural Development","volume":"10","author":"FT Goodfellow","year":"2018","journal-title":"Viruses"},{"key":"pntd.0009183.ref036","first-page":"932019","article-title":"Comparative Analysis of African and Asian Lineage-Derived Zika Virus Strains Reveals Differences in Activation of and Sensitivity to Antiviral Innate Immunity","author":"K Esser-Nobis","journal-title":"J Virol"},{"issue":"4","key":"pntd.0009183.ref037","doi-asserted-by":"crossref","DOI":"10.1128\/mSphere.00292-17","article-title":"Phenotypic Differences between Asian and African Lineage Zika Viruses in Human Neural Progenitor Cells","volume":"2","author":"F Anfasa","year":"2017","journal-title":"mSphere"},{"key":"pntd.0009183.ref038","article-title":"The African Zika virus MR-766 is more virulent and causes more severe brain damage than current","author":"Q Shao","year":"2017","journal-title":"Asian lineage and dengue virus"},{"issue":"1","key":"pntd.0009183.ref039","article-title":"Asian and African Lineage Zika Viruses Show Differential Replication and Innate Immune Responses in Human Dendritic Cells and Macrophages","volume":"9","year":"2019","journal-title":"Scientific reports"},{"issue":"1","key":"pntd.0009183.ref040","article-title":"The African Strain of Zika Virus Causes More Severe in utero Infection Than Asian Strain in a Porcine Fetal Transmission Model","volume":"8","year":"2019","journal-title":"Emerging microbes & infections"},{"issue":"1","key":"pntd.0009183.ref041","article-title":"Zika virus induces astrocyte differentiation in neural stem cells","volume":"24","year":"2018","journal-title":"Journal of neurovirology"},{"issue":"1","key":"pntd.0009183.ref042","article-title":"ZIKV Strains Differentially Affect Survival of Human Fetal Astrocytes versus Neurons and Traffic of ZIKV-Laden Endocytotic Compartments","volume":"9","year":"2019","journal-title":"Scientific reports"},{"issue":"1","key":"pntd.0009183.ref043","first-page":"1","article-title":"Activation of type I interferon antiviral response in human neural stem cells","volume":"10","author":"J-Y Lin","year":"2019","journal-title":"Stem Cell Research & Therapy"},{"issue":"6","key":"pntd.0009183.ref044","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1007\/s00430-019-00588-8","article-title":"Innate immune response in patients with acute Zika virus infection","volume":"208","author":"MHM da Silva","year":"2019","journal-title":"Med Microbiol Immunol"},{"issue":"7362","key":"pntd.0009183.ref045","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1038\/nature10357","article-title":"The aging systemic milieu negatively regulates neurogenesis and cognitive function","volume":"477","author":"SA Villeda","year":"2011","journal-title":"Nature"},{"issue":"8","key":"pntd.0009183.ref046","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1038\/nm.3898","article-title":"beta2-microglobulin is a systemic pro-aging factor that impairs cognitive function and neurogenesis","volume":"21","author":"LK Smith","year":"2015","journal-title":"Nat Med"},{"issue":"1","key":"pntd.0009183.ref047","article-title":"Defective Neuronogenesis in the Absence of Dlx5","volume":"25","year":"2004","journal-title":"Molecular and cellular neurosciences"},{"key":"pntd.0009183.ref048","first-page":"10","article-title":"Distinct Features of Doublecortin as a Marker of Neuronal Migration and Its Implications in Cancer Cell Mobility","author":"AA Ayanlaja","year":"2017","journal-title":"Front Mol Neurosci"},{"key":"pntd.0009183.ref049","first-page":"187","article-title":"Interferon-Alpha Reduces Human Hippocampal Neurogenesis and Increases Apoptosis via Activation of Distinct STAT1-Dependent Mechanisms","volume":"18","author":"A Borsini","year":"2120","journal-title":"Int J Neuropsychopharmacol"},{"key":"pntd.0009183.ref050","first-page":"9","article-title":"IFN gamma regulates proliferation and neuronal differentiation by STAT1 in adult SVZ niche","author":"L Pereira","year":"2015","journal-title":"Front Cell Neurosci"},{"key":"pntd.0009183.ref051","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.1002\/jnr.23987","article-title":"The antiviral cytokine interferon-gamma restricts neural stem\/progenitor cell proliferation through activation of STAT1 and modulation of retinoblastoma protein phosphorylation","volume":"95","author":"A Kulkarni","year":"2017","journal-title":"J Neurosci Res"},{"issue":"4","key":"pntd.0009183.ref052","article-title":"Fludarabine-induced Immunosuppression Is Associated With Inhibition of STAT1 Signaling","volume":"5","year":"1999","journal-title":"Nature medicine"},{"issue":"5","key":"pntd.0009183.ref053","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1093\/oxfordjournals.annonc.a058515","article-title":"Immunosuppressive effects and clinical response of fludarabine in refractory chronic lymphocytic leukemia","volume":"4","author":"L Bergmann","year":"1993","journal-title":"Ann Oncol"},{"issue":"2","key":"pntd.0009183.ref054","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.mcn.2007.03.001","article-title":"STAT5A\/B activity is required in the developing forebrain and spinal cord","volume":"35","author":"K Markham","year":"2007","journal-title":"Mol Cell Neurosci"},{"key":"pntd.0009183.ref055","volume-title":"Journal of Neuroscience Research","year":"2020"},{"key":"pntd.0009183.ref056","unstructured":"Frontiers | The Dual Nature of Type I and Type II Interferons | Immunology. 2020."},{"key":"pntd.0009183.ref057","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1128\/CMR.14.4.778-809.2001","article-title":"Antiviral Actions of Interferons","volume":"14","author":"CE Samuel","year":"2001","journal-title":"Clin Microbiol Rev"},{"issue":"6","key":"pntd.0009183.ref058","first-page":"407","article-title":"G, ZHENG D, TANG H, CHENG G. The host type I interferon response to viral and bacterial infections","volume":"15","author":"CHEN PERRY AK","year":"2020","journal-title":"Cell Research"},{"key":"pntd.0009183.ref059","author":"AP Costa-Pereira","year":"2002","journal-title":"The Antiviral Response to Gamma Interferon"},{"issue":"12","key":"pntd.0009183.ref060","doi-asserted-by":"crossref","first-page":"1766","DOI":"10.15252\/embr.201642627","article-title":"Zika virus inhibits type-I interferon production and downstream signaling","volume":"17","author":"A Kumar","year":"2016","journal-title":"EMBO Rep"},{"issue":"7","key":"pntd.0009183.ref061","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.1002\/eji.201847483","article-title":"Infection with a Brazilian isolate of Zika virus generates RIG-I stimulatory RNA and the viral NS5 protein blocks type I IFN induction and signaling","volume":"48","author":"J Hertzog","year":"2018","journal-title":"Eur J Immunol"},{"issue":"6","key":"pntd.0009183.ref062","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1016\/j.chom.2016.05.009","article-title":"Zika Virus Targets Human STAT2 to Inhibit Type I Interferon Signaling","volume":"19","author":"A Grant","year":"2016","journal-title":"Cell Host Microbe"},{"issue":"1","key":"pntd.0009183.ref063","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1038\/s41467-017-02816-2","article-title":"An evolutionary NS1 mutation enhances Zika virus evasion of host interferon induction","volume":"9","author":"H Xia","year":"2018","journal-title":"Nat Commun"},{"key":"pntd.0009183.ref064","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.virol.2018.11.009","article-title":"Zika virus NS5 protein antagonizes type I interferon production via blocking TBK1 activation","volume":"527","author":"S Lin","year":"2019","journal-title":"Virology"},{"key":"pntd.0009183.ref065","first-page":"187","article-title":"Fludarabine in the treatment of chronic lymphocytic leukemia: a review","volume":"5","author":"F Ricci","year":"2009","journal-title":"Ther Clin Risk Manag"},{"key":"pntd.0009183.ref066","doi-asserted-by":"crossref","first-page":"2062","DOI":"10.1182\/blood-2007-05-091207","article-title":"STAT1 signaling modulates HIV-1\u2013induced inflammatory responses and leukocyte transmigration across the blood-brain barrier","volume":"111","author":"A Chaudhuri","year":"2008","journal-title":"Blood"},{"key":"pntd.0009183.ref067","unstructured":"Kanai T, Stanford University DoIaA, Department of Pediatrics, Stanford, United States, tkanai@stanford.edu, Jenks J, Stanford University DoIaA, Department of Pediatrics, Stanford, United States, Jenjenks@stnford.edu, et al. The STAT5b Pathway Defect and Autoimmunity. Frontiers in Immunology. 2012;3."},{"key":"pntd.0009183.ref068","author":"L Campanati","year":"2016","journal-title":"The Impact of African and Brazilian Zika virus isolates on neuroprogenitors"},{"key":"pntd.0009183.ref069","unstructured":"Frontiers | The Transcriptional and Protein Profile From Human Infected Neuroprogenitor Cells Is Strongly Correlated to Zika Virus Microcephaly Cytokines Phenotype Evidencing a Persistent Inflammation in the CNS | Immunology. 2020."},{"key":"pntd.0009183.ref070","doi-asserted-by":"crossref","first-page":"64","DOI":"10.3389\/fncel.2019.00064","article-title":"Zika Virus Impairs Neurogenesis and Synaptogenesis Pathways in Human Neural Stem Cells and Neurons","volume":"13","author":"L Rosa-Fernandes","year":"2019","journal-title":"Front Cell Neurosci"},{"issue":"3","key":"pntd.0009183.ref071","article-title":"G. Modulating Effect of Cytokines on Mechanisms of Synaptic Plasticity in the Brain","volume":"82","author":"OV SG L","year":"2017","journal-title":"Biochemistry Biokhimiia"},{"issue":"3","key":"pntd.0009183.ref072","article-title":"The role of inflammatory cytokines as key modulators of neurogenesis","volume":"38","year":"2015","journal-title":"Trends in neurosciences"},{"issue":"5","key":"pntd.0009183.ref073","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1002\/cne.21974","article-title":"Equal numbers of neuronal and nonneuronal cells make the human brain an isometrically scaled-up primate brain","volume":"513","author":"FA Azevedo","year":"2009","journal-title":"J Comp Neurol"},{"issue":"3","key":"pntd.0009183.ref074","article-title":"Regional Astrocyte IFN Signaling Restricts Pathogenesis During Neurotropic Viral Infection","volume":"127","year":"2017","journal-title":"The Journal of clinical investigation"},{"key":"pntd.0009183.ref075","first-page":"3","article-title":"Viral CNS Infections: Role of Glial Pattern Recognition Receptors in Neuroinflammation","year":"2012","journal-title":"Frontiers in microbiology"},{"issue":"8","key":"pntd.0009183.ref076","doi-asserted-by":"crossref","first-page":"2161","DOI":"10.1523\/JNEUROSCI.3124-16.2017","article-title":"Zika Virus Targeting in the Developing Brain","volume":"37","author":"AN van den Pol","year":"2017","journal-title":"J Neurosci"},{"issue":"2","key":"pntd.0009183.ref077","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1038\/s41590-017-0021-y","article-title":"Astrocytes decrease adult neurogenesis during virus-induced memory dysfunction via IL-1","volume":"19","author":"C Garber","year":"2018","journal-title":"Nature Immunology"}],"updated-by":[{"DOI":"10.1371\/journal.pntd.0009183","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,3,15]],"date-time":"2021-03-15T00:00:00Z","timestamp":1615766400000}}],"container-title":["PLOS Neglected Tropical Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0009183","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,3,15]],"date-time":"2021-03-15T17:42:57Z","timestamp":1615830177000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0009183"}},"subtitle":[],"editor":[{"given":"Gregory","family":"Gromowski","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2021,3,3]]},"references-count":77,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2021,3,3]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pntd.0009183","relation":{"new_version":[{"id-type":"doi","id":"10.1371\/journal.pntd.0009183","asserted-by":"object"}]},"ISSN":["1935-2735"],"issn-type":[{"value":"1935-2735","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,3]]}}}