{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T20:33:39Z","timestamp":1790800419159,"version":"4.1.0"},"reference-count":51,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2018,11,17]],"date-time":"2018-11-17T00:00:00Z","timestamp":1542412800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["CIHR MOP-125903"],"award-info":[{"award-number":["CIHR MOP-125903"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["PJT-148699"],"award-info":[{"award-number":["PJT-148699"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["ZV1-149782"],"award-info":[{"award-number":["ZV1-149782"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Zika virus (ZIKV) infection and persistence during pregnancy can lead to microcephaly and other fetal neurological disorders collectively known as Congenital Zika Syndrome. The immunological and virological events that contribute to the establishment of persistent ZIKV infection in humans are unclear though. Here we show that human fetal astrocytes (HFAs), the most abundant cell type in the central nervous system, become persistently infected with ZIKV resulting in continuous viral shedding for at least one month; a process that is facilitated by TIM\/TAM receptors. HFAs are relatively resistant to ZIKV-induced apoptosis, a factor that may be important for chronic infection of these cells. Once infection was established, interferon treatment did not reduce virus replication. Moreover, the fact that the innate immune system was highly activated in persistently infected HFAs indicates that the virus can thrive in the presence of a sustained antiviral response. RNAseq analyses of persistently infected cells revealed that ZIKV alters host gene expression in a manner that could affect developmental processes. Conversely, data from sequencing of ZIKV genomes in persistently infected HFAs suggest that adaptive mutations were not required for establishing chronic infection. Based on these results, we postulate that HFAs are reservoirs for ZIKV in the fetal brain and that moderate apoptosis combined with inefficient antiviral response from these cells may contribute to the establishment of chronic brain infection associated with the ZIKV neurodevelopmental abnormalities.<\/jats:p>","DOI":"10.3390\/v10110646","type":"journal-article","created":{"date-parts":[[2018,11,23]],"date-time":"2018-11-23T03:41:31Z","timestamp":1542944491000},"page":"646","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":64,"title":["Human Fetal Astrocytes Infected with Zika Virus Exhibit Delayed Apoptosis and Resistance to Interferon: Implications for Persistence"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5128-6542","authenticated-orcid":false,"given":"Daniel","family":"Limonta","sequence":"first","affiliation":[{"name":"Department of Cell Biology, University of Alberta, Edmonton, Alberta, T6G 2H7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Jovel","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Alberta, Edmonton, Alberta, T6G 2E1 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anil","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, University of Alberta, Edmonton, Alberta, T6G 2H7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana M.","family":"Airo","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology &amp; Immunology, University of Alberta, Edmonton, Alberta, T6G 2E1 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shangmei","family":"Hou","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, University of Alberta, Edmonton, Alberta, T6G 2H7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9443-9775","authenticated-orcid":false,"given":"Leina","family":"Saito","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Alberta, Edmonton, Alberta, T6G 2E1 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Branton","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Alberta, Edmonton, Alberta, T6G 2E1 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6108-5560","authenticated-orcid":false,"given":"Gane","family":"Ka-Shu Wong","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Alberta, Edmonton, Alberta, T6G 2E1 Canada"},{"name":"Department of Biological Sciences, University of Alberta, Edmonton, Alberta, T6G 2E9, Canada"},{"name":"Beijing Genomics Institute, Beishan Industrial Zone, Yantian District, Shenzhen, 518083, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Mason","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Alberta, Edmonton, Alberta, T6G 2E1 Canada"},{"name":"Department of Medical Microbiology &amp; Immunology, University of Alberta, Edmonton, Alberta, T6G 2E1 Canada"},{"name":"Women &amp; Children\u2019s Health Research Institute, University of Alberta, Edmonton, Alberta, T6G 1C9, Canada"},{"name":"Li Ka Shing Institute of Virology, University of Alberta, Edmonton, Alberta, T6G 2E1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5131-9711","authenticated-orcid":false,"given":"Christopher","family":"Power","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Alberta, Edmonton, Alberta, T6G 2E1 Canada"},{"name":"Department of Medical Microbiology &amp; Immunology, University of Alberta, Edmonton, Alberta, T6G 2E1 Canada"},{"name":"Women &amp; Children\u2019s Health Research Institute, University of Alberta, Edmonton, Alberta, T6G 1C9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom C.","family":"Hobman","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, University of Alberta, Edmonton, Alberta, T6G 2H7, Canada"},{"name":"Department of Medical Microbiology &amp; Immunology, University of Alberta, Edmonton, Alberta, T6G 2E1 Canada"},{"name":"Women &amp; Children\u2019s Health Research Institute, University of Alberta, Edmonton, Alberta, T6G 1C9, Canada"},{"name":"Li Ka Shing Institute of Virology, University of Alberta, Edmonton, Alberta, T6G 2E1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,11,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1038\/s41586-018-0446-y","article-title":"The emergence of Zika virus and its new clinical syndromes","volume":"560","author":"Pierson","year":"2018","journal-title":"Nature"},{"key":"ref_2","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":"Brasil","year":"2016","journal-title":"N. 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