{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T02:59:33Z","timestamp":1776135573170,"version":"3.50.1"},"reference-count":121,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,29]],"date-time":"2022-12-29T00:00:00Z","timestamp":1672272000000},"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 (CIHR)","doi-asserted-by":"publisher","award":["PSS-177951"],"award-info":[{"award-number":["PSS-177951"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Canadian Foundation for Innovation (CFI)","award":["PSS-177951"],"award-info":[{"award-number":["PSS-177951"]}]},{"name":"CIHR","award":["PSS-177951"],"award-info":[{"award-number":["PSS-177951"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>(1) Background: Zika virus (ZIKV), an arbo-flavivirus, is transmitted via Aeges aegyptii mosquitoes Following its major outbreaks in 2013, 2014 and 2016, WHO declared it a Public Health Emergency of International Concern. Symptoms of ZIKV infection include acute fever, conjunctivitis, headache, muscle &amp; joint pain and malaise. Cases of its transmission also have been reported via perinatal, sexual and transfusion transmission. ZIKV pathologies include meningo-encephalitis and myelitis in the central nervous system (CNS) and Guillain-Barr\u00e9 syndrome and acute transient polyneuritis in the peripheral nervous system (PNS). Drugs like azithromycin have been tested as inhibitors of ZIKV infection but no vaccines or treatments are currently available. Astrocytes are the most abundant cells in the CNS and among the first cells in CNS infected by ZIKV; (2) Methods: We previously used SOMAScan proteomics to study ZIKV-infected astrocytic cells. Here, we use mass spectrometric analyses to further explain dysregulations in the cellular expression profile of glioblastoma astrocytoma U251 cells. We also knocked down (KD) some of the U251 cellular proteins using siRNAs and observed the impact on ZIKV replication and infectivity; (3) Results &amp; Conclusions: The top ZIKV dysregulated cellular networks were antimicrobial response, cell death, and energy production while top dysregulated functions were antigen presentation, viral replication and cytopathic impact. Th1 and interferon signaling pathways were among the top dysregulated canonical pathways. siRNA-mediated KD of HLA-A, IGFBP5, PSMA2 and HSPA5 increased ZIKV titers and protein synthesis, indicating they are ZIKV restriction factors. ZIKV infection also restored HLA-A expression in HLA-A KD cells by 48 h post-infection, suggesting interactions between this gene product and ZIKV.<\/jats:p>","DOI":"10.3390\/v15010097","type":"journal-article","created":{"date-parts":[[2022,12,30]],"date-time":"2022-12-30T05:15:53Z","timestamp":1672377353000},"page":"97","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["HLA-A, HSPA5, IGFBP5 and PSMA2 Are Restriction Factors for Zika Virus Growth in Astrocytic Cells"],"prefix":"10.3390","volume":"15","author":[{"given":"Affan A.","family":"Sher","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology & Infectious Diseases, University of Manitoba, Winnipeg, MB R3E 0J9, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying Tenny","family":"Lao","sequence":"additional","affiliation":[{"name":"Manitoba Centre for Proteomics & Systems Biology, University of Manitoba, Winnipeg, MB R3E 3P4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7667-8430","authenticated-orcid":false,"given":"Kevin M.","family":"Coombs","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology & Infectious Diseases, University of Manitoba, Winnipeg, MB R3E 0J9, Canada"},{"name":"Manitoba Centre for Proteomics & Systems Biology, University of Manitoba, Winnipeg, MB R3E 3P4, Canada"},{"name":"Children\u2019s Hospital Research Institute of Manitoba, Winnipeg, MB R3E 3P4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1080\/01652176.2016.1188333","article-title":"Zika virus\u2013emergence, evolution, pathology, diagnosis, and control: Current global scenario and future perspectives\u2014A comprehensive review","volume":"36","author":"Singh","year":"2016","journal-title":"Vet. 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