{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T23:36:29Z","timestamp":1785368189718,"version":"3.55.0"},"reference-count":93,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,11,27]],"date-time":"2021-11-27T00:00:00Z","timestamp":1637971200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01GM139971"],"award-info":[{"award-number":["R01GM139971"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006827","name":"Florida Department of Health","doi-asserted-by":"publisher","award":["7ZK06"],"award-info":[{"award-number":["7ZK06"]}],"id":[{"id":"10.13039\/100006827","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Zika virus (ZIKV) became a global health concern in 2016 due to its links to congenital microcephaly and other birth defects. Flaviviruses, including ZIKV, reorganize the endoplasmic reticulum (ER) to form a viroplasm, a compartment where virus particles are assembled. Microtubules (MTs) and microtubule-organizing centers (MTOCs) coordinate structural and trafficking functions in the cell, and MTs also support replication of flaviviruses. Here we investigated the roles of MTs and the cell\u2019s MTOCs on ZIKV viroplasm organization and virus production. We show that a toroidal-shaped viroplasm forms upon ZIKV infection, and MTs are organized at the viroplasm core and surrounding the viroplasm. We show that MTs are necessary for viroplasm organization and impact infectious virus production. In addition, the centrosome and the Golgi MTOC are closely associated with the viroplasm, and the centrosome coordinates the organization of the ZIKV viroplasm toroidal structure. Surprisingly, viroplasm formation and virus production are not significantly impaired when infected cells have no centrosomes and impaired Golgi MTOC, and we show that MTs are anchored to the viroplasm surface in these cells. We propose that the viroplasm is a site of MT organization, and the MTs organized at the viroplasm are sufficient for efficient virus production.<\/jats:p>","DOI":"10.3390\/cells10123335","type":"journal-article","created":{"date-parts":[[2021,11,29]],"date-time":"2021-11-29T01:49:58Z","timestamp":1638150598000},"page":"3335","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Coordination of Zika Virus Infection and Viroplasm Organization by Microtubules and Microtubule-Organizing Centers"],"prefix":"10.3390","volume":"10","author":[{"given":"Rebecca A.","family":"Buchwalter","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, Florida State University, Tallahassee, FL 32306, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah C.","family":"Ogden","sequence":"additional","affiliation":[{"name":"Department of Biological Science, Florida State University, Tallahassee, FL 32306, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara B.","family":"York","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Florida State University, Tallahassee, FL 32306, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8228-7487","authenticated-orcid":false,"given":"Li","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Florida State University, Tallahassee, FL 32306, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunfeng","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Florida State University, Tallahassee, FL 32306, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christy","family":"Hammack","sequence":"additional","affiliation":[{"name":"Department of Biological Science, Florida State University, Tallahassee, FL 32306, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yichen","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Biological Science, Florida State University, Tallahassee, FL 32306, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jieyan V.","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Florida State University, Tallahassee, FL 32306, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allaura S.","family":"Cone","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Florida State University, Tallahassee, FL 32306, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0836-2108","authenticated-orcid":false,"suffix":"Jr.","given":"David G.","family":"Meckes","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Florida State University, Tallahassee, FL 32306, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hengli","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Biological Science, Florida State University, Tallahassee, FL 32306, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7455-7483","authenticated-orcid":false,"given":"Timothy L.","family":"Megraw","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Florida State University, Tallahassee, FL 32306, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1056\/NEJMra1808246","article-title":"Zika virus infection\u2014After the pandemic","volume":"381","author":"Musso","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1056\/NEJMoa1600651","article-title":"Zika Virus Associated with Microcephaly","volume":"374","author":"Mlakar","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_3","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":"Tang","year":"2016","journal-title":"Cell Stem Cell"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.chom.2017.01.004","article-title":"Zika Virus Pathogenesis and Tissue Tropism","volume":"21","author":"Miner","year":"2017","journal-title":"Cell Host Microbe"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"405","DOI":"10.3201\/eid2303.161499","article-title":"Zika Virus RNA Replication and Persistence in Brain and Placental Tissue","volume":"23","author":"Bhatnagar","year":"2017","journal-title":"Emerg. Infect. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Romero-Brey, I., and Bartenschlager, R. (2016). Endoplasmic Reticulum: The Favorite Intracellular Niche for Viral Replication and Assembly. Viruses, 8.","DOI":"10.3390\/v8060160"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Rothan, H.A., and Kumar, M. (2019). Role of Endoplasmic Reticulum-Associated Proteins in Flavivirus Replication and Assembly Complexes. Pathogens, 8.","DOI":"10.3390\/pathogens8030148"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Rajah, M.M., Monel, B., and Schwartz, O. (2020). The entanglement between flaviviruses and ER-shaping proteins. PLoS Pathog., 16.","DOI":"10.1371\/journal.ppat.1008389"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2826","DOI":"10.3390\/v6072826","article-title":"Membranous Replication Factories Induced by Plus-Strand RNA Viruses","volume":"6","author":"Bartenschlager","year":"2014","journal-title":"Viruses"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/s12929-020-0618-6","article-title":"Endoplasmic reticulum: A focal point of Zika virus infection","volume":"27","author":"Ropidi","year":"2020","journal-title":"J. Biomed. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.chom.2009.03.007","article-title":"Composition and Three-Dimensional Architecture of the Dengue Virus Replication and Assembly Sites","volume":"5","author":"Welsch","year":"2009","journal-title":"Cell Host Microbe"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"6469","DOI":"10.1128\/JVI.03456-12","article-title":"Three-Dimensional Architecture of Tick-Borne Encephalitis Virus Replication Sites and Trafficking of the Replicated RNA","volume":"87","author":"Miorin","year":"2013","journal-title":"J. Virol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"10438","DOI":"10.1128\/JVI.00986-10","article-title":"The Endoplasmic Reticulum Provides the Membrane Platform for Biogenesis of the Flavivirus Replication Complex","volume":"84","author":"Gillespie","year":"2010","journal-title":"J. Virol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"10787","DOI":"10.1128\/JVI.75.22.10787-10799.2001","article-title":"Assembly and Maturation of the Flavivirus Kunjin Virus Appear To Occur in the Rough Endoplasmic Reticulum and along the Secretory Pathway, Respectively","volume":"75","author":"Mackenzie","year":"2001","journal-title":"J. Virol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2113","DOI":"10.1016\/j.celrep.2017.02.014","article-title":"Ultrastructural Characterization of Zika Virus Replication Factories","volume":"18","author":"Cortese","year":"2017","journal-title":"Cell Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"eaaf4382","DOI":"10.1126\/science.aaf4382","article-title":"Liquid phase condensation in cell physiology and disease","volume":"357","author":"Shin","year":"2017","journal-title":"Science"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1777","DOI":"10.1007\/s00705-008-0183-x","article-title":"Vimentin is required for dengue virus serotype 2 infection but microtubules are not necessary for this process","volume":"153","author":"Chen","year":"2008","journal-title":"Arch. Virol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Shrivastava, N., Sripada, S., Kaur, J., Shah, P.S., and Cecilia, D. (2011). Insights into the Internalization and Retrograde Trafficking of Dengue 2 Virus in BHK-21 Cells. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0025229"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1007\/BF01310739","article-title":"Involvement of microtubules in Kunjin virus replication","volume":"97","author":"Hong","year":"1987","journal-title":"Arch. Virol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1649","DOI":"10.1099\/vir.0.010058-0","article-title":"Morphological changes in human neural cells following tick-borne encephalitis virus infection","volume":"90","author":"Ruzek","year":"2009","journal-title":"J. Gen. Virol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1002\/jmv.2201","article-title":"Trafficking mechanism of west Nile (Sarafend) virus structural proteins","volume":"67","author":"Chu","year":"2002","journal-title":"J. Med. Virol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"427814","DOI":"10.1155\/2015\/427814","article-title":"Interaction between flavivirus and cytoskeleton during virus replication","volume":"2015","author":"Foo","year":"2015","journal-title":"BioMed Res. Int."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1007\/s12250-019-00086-4","article-title":"The Role of Host Cytoskeleton in Flavivirus Infection","volume":"34","author":"Zhang","year":"2019","journal-title":"Virol. Sin."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.virol.2019.04.008","article-title":"Comparative analysis of viral entry for Asian and African lineages of Zika virus","volume":"533","author":"Rinkenberger","year":"2019","journal-title":"Virology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"242","DOI":"10.3389\/fmicb.2020.00242","article-title":"Characterization of Zika Virus Endocytic Pathways in Human Glioblastoma Cells","volume":"11","author":"Li","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e2101713118","DOI":"10.1073\/pnas.2101713118","article-title":"Zika virus employs the host antiviral RNase L protein to support replication factory assembly","volume":"118","author":"Whelan","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"4246","DOI":"10.1073\/pnas.1720032115","article-title":"Flavivirus internalization is regulated by a size-dependent endocytic pathway","volume":"115","author":"Hackett","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Buchwalter, R.A., Chen, J.V., Zheng, Y., and Megraw, T.L. (2016). Centrosome in Cell Division, Development and Disease. eLS, 1\u201312.","DOI":"10.1002\/9780470015902.a0020872"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1038\/nrm4062","article-title":"Centrosome function and assembly in animal cells","volume":"16","author":"Conduit","year":"2015","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.ceb.2016.09.003","article-title":"Microtubule-organizing centers: From the centrosome to non-centrosomal sites","volume":"44","author":"Sanchez","year":"2016","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3012","DOI":"10.1242\/dev.153171","article-title":"Microtubule organization, dynamics and functions in differentiated cells","volume":"144","author":"Muroyama","year":"2017","journal-title":"Development"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Tillery, M.M.L., Blake-Hedges, C., Zheng, Y., Buchwalter, R.A., and Megraw, T.L. (2018). Centrosomal and Non-Centrosomal Microtubule-Organizing Centers (MTOCs) in Drosophila melanogaster. Cells, 7.","DOI":"10.3390\/cells7090121"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.tcb.2017.10.005","article-title":"Microtubule-Organizing Centers: Towards a Minimal Parts List","volume":"28","author":"Paz","year":"2018","journal-title":"Trends Cell Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"R506","DOI":"10.1016\/j.cub.2021.01.042","article-title":"Microtubule organization across cell types and states","volume":"31","author":"Sallee","year":"2021","journal-title":"Curr. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1146\/annurev-cellbio-100616-060615","article-title":"Microtubule-Organizing Centers","volume":"33","author":"Wu","year":"2017","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1016\/j.tcb.2018.02.011","article-title":"Coming into Focus: Mechanisms of Microtubule Minus-End Organization","volume":"28","author":"Martin","year":"2018","journal-title":"Trends Cell Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"135806","DOI":"10.1016\/j.neulet.2021.135806","article-title":"To nucleate or not, that is the question in neurons","volume":"751","author":"Weiner","year":"2021","journal-title":"Neurosci. Lett."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.conb.2019.01.003","article-title":"Microtubule control of functional architecture in neurons","volume":"57","author":"Kelliher","year":"2019","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"431","DOI":"10.3389\/fnins.2015.00431","article-title":"Nucleation and dynamics of Golgi-derived microtubules","volume":"9","author":"Sanders","year":"2015","journal-title":"Frontiers in neuroscience"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1007\/s00418-013-1119-4","article-title":"Golgi as an MTOC: Making microtubules for its own good","volume":"140","author":"Zhu","year":"2013","journal-title":"Histochem. Cell Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1016\/j.tcb.2020.07.004","article-title":"Golgi Outposts Nucleate Microtubules in Cells with Specialized Shapes","volume":"30","author":"Valenzuela","year":"2020","journal-title":"Trends Cell Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1146\/annurev-genom-083117-021441","article-title":"The Genetics of Primary Microcephaly","volume":"19","author":"Jayaraman","year":"2018","journal-title":"Annu. Rev. Genom. Hum. Genet."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1091\/mbc.E17-03-0192","article-title":"Same but different: Pleiotropy in centrosome-related microcephaly","volume":"29","author":"Schoborg","year":"2018","journal-title":"Mol. Biol. Cell"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"570830","DOI":"10.3389\/fneur.2020.570830","article-title":"Dissecting the Genetic and Etiological Causes of Primary Microcephaly","volume":"11","author":"Jean","year":"2020","journal-title":"Front. Neurol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1016\/j.tcb.2011.04.007","article-title":"Cdk5rap2 exposes the centrosomal root of microcephaly syndromes","volume":"21","author":"Megraw","year":"2011","journal-title":"Trends Cell Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.mcp.2015.05.015","article-title":"What next-generation sequencing (NGS) technology has enabled us to learn about primary autosomal recessive microcephaly (MCPH)","volume":"29","author":"Kaindl","year":"2015","journal-title":"Mol. Cell. Probes"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e7","DOI":"10.1017\/S0016672318000046","article-title":"Comprehensive review on the molecular genetics of autosomal recessive primary microcephaly (MCPH)","volume":"100","author":"Naveed","year":"2018","journal-title":"Genet. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/978-3-319-57127-0_2","article-title":"Consequences of Centrosome Dysfunction During Brain Development","volume":"1002","author":"Nano","year":"2017","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Faheem, M., Naseer, M.I., Rasool, M., Chaudhary, A.G., Kumosani, T.A., Ilyas, A.M., Pushparaj, P.N., Ahmed, F., Algahtani, H.A., and Al-Qahtani, M.H. (2015). Molecular genetics of human primary microcephaly: An overview. BMC Med. Genom., 8.","DOI":"10.1186\/1755-8794-8-S1-S4"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e51094","DOI":"10.15252\/embr.202051094","article-title":"The Golgi microtubules regulate single cell durotaxis","volume":"22","author":"Rong","year":"2021","journal-title":"EMBO Rep."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.devcel.2016.08.009","article-title":"Molecular Pathway of Microtubule Organization at the Golgi Apparatus","volume":"39","author":"Wu","year":"2016","journal-title":"Dev. Cell"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1038\/emboj.2009.47","article-title":"Microtubule nucleation at the cis-side of the Golgi apparatus requires AKAP450 and GM130","volume":"28","author":"Rivero","year":"2009","journal-title":"EMBO J."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1016\/j.devcel.2007.04.002","article-title":"Asymmetric CLASP-Dependent Nucleation of Noncentrosomal Microtubules at the trans-Golgi Network","volume":"12","author":"Efimov","year":"2007","journal-title":"Dev. Cell"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2339","DOI":"10.1016\/j.cub.2019.06.032","article-title":"Regulation of Glucose-Dependent Golgi-Derived Microtubules by cAMP\/EPAC2 Promotes Secretory Vesicle Biogenesis in Pancreatic \u03b2 Cells","volume":"29","author":"Trogden","year":"2019","journal-title":"Curr. Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1038\/ncb1920","article-title":"Golgi-derived CLASP-dependent microtubules control Golgi organization and polarized trafficking in motile cells","volume":"11","author":"Miller","year":"2009","journal-title":"Nat. Cell Biol."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Vergarajauregui, S., Becker, R., Steffen, U., Sharkova, M., Esser, T., Petzold, J., Billing, F., Kapiloff, M.S., Schett, G., and Thievessen, I. (2020). AKAP6 orchestrates the nuclear envelope microtubule-organizing center by linking golgi and nucleus via AKAP9. eLife, 9.","DOI":"10.7554\/eLife.61669"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1091\/mbc.E21-02-0060","article-title":"Centriole and Golgi microtubule nucleation are dispensable for the migration of human neutrophil-like cells","volume":"3","author":"Klemm","year":"2021","journal-title":"Mol. Biol. Cell"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e45942","DOI":"10.15252\/embr.201845942","article-title":"The dual role of the centrosome in organizing the microtubule network in interphase","volume":"19","author":"Gavilan","year":"2018","journal-title":"EMBO Rep."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"6334","DOI":"10.1038\/onc.2008.254","article-title":"PP2A-dependent disruption of centrosome replication and cytoskeleton organization in Drosophila by SV40 small tumor antigen","volume":"27","author":"Kotadia","year":"2008","journal-title":"Oncogene"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1158\/1541-7786.159.2.3","article-title":"Mitotic aberration coupled with centrosome amplification is induced by hepatitis B virus X oncoprotein via the Ras-mitogen-activated protein\/extracellular signal-regulated kinase-mitogen-activated protein pathway","volume":"2","author":"Yun","year":"2004","journal-title":"Mol. Cancer Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"14257","DOI":"10.1038\/ncomms14257","article-title":"Epstein\u2013Barr virus particles induce centrosome amplification and chromosomal instability","volume":"8","author":"Shumilov","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"18974","DOI":"10.1073\/pnas.0506659103","article-title":"Abnormal centrosome amplification in cells through the targeting of Ran-binding protein-1 by the human T cell leukemia virus type-1 Tax oncoprotein","volume":"102","author":"Peloponese","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"10002","DOI":"10.1073\/pnas.170093297","article-title":"The human papillomavirus type 16 E6 and E7 oncoproteins cooperate to induce mitotic defects and genomic instability by uncoupling centrosome duplication from the cell division cycle","volume":"97","author":"Duensing","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_64","first-page":"1430","article-title":"E1A deregulates the centrosome cycle in a Ran GTPase-dependent manner","volume":"63","author":"Mangiacasale","year":"2003","journal-title":"Cancer Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e00538-17","DOI":"10.1128\/JVI.00538-17","article-title":"Microtubule Regulation and Function during Virus Infection","volume":"91","author":"Naghavi","year":"2017","journal-title":"J. Virol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"e0082121","DOI":"10.1128\/JVI.00821-21","article-title":"Human cytomegalovirus exploits TACC3 to control microtubule dynamics and late stages of infection","volume":"95","author":"Furey","year":"2021","journal-title":"J. Virol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.devcel.2018.03.010","article-title":"The HCMV Assembly Compartment Is a Dynamic Golgi-Derived MTOC that Controls Nuclear Rotation and Virus Spread","volume":"45","author":"Procter","year":"2018","journal-title":"Dev. Cell"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.stem.2016.12.005","article-title":"Recent Zika Virus Isolates Induce Premature Differentiation of Neural Progenitors in Human Brain Organoids","volume":"20","author":"Gabriel","year":"2017","journal-title":"Cell Stem Cell"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"160231","DOI":"10.1098\/rsob.160231","article-title":"Zika virus causes supernumerary foci with centriolar proteins and impaired spindle positioning","volume":"7","author":"Wolf","year":"2017","journal-title":"Open Biol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2576","DOI":"10.1016\/j.celrep.2016.08.038","article-title":"Zika Virus Disrupts Phospho-TBK1 Localization and Mitosis in Human Neuroepithelial Stem Cells and Radial Glia","volume":"16","author":"Onorati","year":"2016","journal-title":"Cell Rep."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"39775","DOI":"10.1038\/srep39775","article-title":"Zika virus infection induces mitosis abnormalities and apoptotic cell death of human neural progenitor cells","volume":"6","author":"Souza","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"18742","DOI":"10.1074\/jbc.RA119.010973","article-title":"Zika virus increases mind bomb 1 levels, causing degradation of pericentriolar material 1 (PCM1) and dispersion of PCM1-containing granules from the centrosome","volume":"294","author":"Wen","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Kodani, A., Knopp, K., Di Lullo, E., Retallack, H., Kriegstein, A., DeRisi, J., and Reiter, J. (2020). Zika virus alters centrosome organization to suppress the innate immune response. bioRxiv.","DOI":"10.1101\/2020.09.15.298083"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1126\/science.aaa5111","article-title":"Reversible centriole depletion with an inhibitor of Polo-like kinase 4","volume":"348","author":"Wong","year":"2015","journal-title":"Science"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"e00638-19","DOI":"10.1128\/JVI.00638-19","article-title":"Zika Virus Infection Induces DNA Damage Response in Human Neural Progenitors That Enhances Viral Replication","volume":"93","author":"Hammack","year":"2019","journal-title":"J. Virol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.jviromet.2017.04.011","article-title":"Development of standard methods for Zika virus propagation, titration, and purification","volume":"246","author":"Coelho","year":"2017","journal-title":"J. Virol. Methods"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1038\/nm.4184","article-title":"Identification of small-molecule inhibitors of Zika virus infection and induced neural cell death via a drug repurposing screen","volume":"22","author":"Xu","year":"2016","journal-title":"Nat. Med."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2281","DOI":"10.1038\/nprot.2013.143","article-title":"Genome engineering using the CRISPR-Cas9 system","volume":"8","author":"Ran","year":"2013","journal-title":"Nat. Protoc."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.jviromet.2016.07.014","article-title":"Detection of Zika virus by SYBR green one-step real-time RT-PCR","volume":"236","author":"Xu","year":"2016","journal-title":"J. Virol. Methods"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"e0019221","DOI":"10.1128\/mSphere.00192-21","article-title":"Zika Virus Hijacks Extracellular Vesicle Tetraspanin Pathways for Cell-to-Cell Transmission","volume":"6","author":"York","year":"2021","journal-title":"mSphere"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1928","DOI":"10.1016\/j.cub.2017.05.090","article-title":"A Splice Variant of Centrosomin Converts Mitochondria to Microtubule-Organizing Centers","volume":"27","author":"Chen","year":"2017","journal-title":"Curr. Biol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1097\/NEN.0000000000000212","article-title":"Overexpression and Nucleolar Localization of \u03b3-Tubulin Small Complex Proteins GCP2 and GCP3 in Glioblastoma","volume":"74","author":"Caracciolo","year":"2015","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1995","DOI":"10.1091\/mbc.12.7.1995","article-title":"Microtubule-dependent Changes in Assembly of Microtubule Motor Proteins and Mitotic Spindle Checkpoint Proteins at PtK1 Kinetochores","volume":"12","author":"Hoffman","year":"2001","journal-title":"Mol. Biol. Cell"},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Lopez-Denman, A.J., and MacKenzie, J.M. (2017). The IMPORTance of the Nucleus during Flavivirus Replication. Viruses, 9.","DOI":"10.3390\/v9010014"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1038\/s41580-020-0214-3","article-title":"The tubulin code and its role in controlling microtubule properties and functions","volume":"21","author":"Janke","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1038\/ncb2746","article-title":"Centrosome amplification causes microcephaly","volume":"15","author":"Marthiens","year":"2013","journal-title":"Nat. Cell Biol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1931","DOI":"10.1016\/j.cell.2018.11.028","article-title":"Comparative Flavivirus-Host Protein Interaction Mapping Reveals Mechanisms of Dengue and Zika Virus Pathogenesis","volume":"175","author":"Shah","year":"2018","journal-title":"Cell"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"2242","DOI":"10.1074\/mcp.TIR118.000800","article-title":"Global Interactomics Uncovers Extensive Organellar Targeting by Zika Virus","volume":"17","author":"Coyaud","year":"2018","journal-title":"Mol. Cell. Proteom."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Golubeva, V.A., Nepomuceno, T.C., De Gregoriis, G., Mesquita, R.D., Li, X., Dash, S., Garcez, P.P., Suarez-Kurtz, G., Izumi, V., and Koomen, J. (2020). Network of Interactions between ZIKA Virus Non-Structural Proteins and Human Host Proteins. Cells, 9.","DOI":"10.3390\/cells9010153"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"012187","DOI":"10.1074\/mcp.M111.012187","article-title":"A Physical Interaction Network of Dengue Virus and Human Proteins","volume":"10","author":"Khadka","year":"2011","journal-title":"Mol. Cell. Proteom."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Le Breton, M., Meyniel-Schicklin, L., Deloire, A., Coutard, B., Canard, B., de Lamballerie, X., Andre, P., Rabourdin-Combe, C., Lotteau, V., and Davoust, N. (2011). Flavivirus NS3 and NS5 proteins interaction network: A high-throughput yeast two-hybrid screen. BMC Microbiol., 11.","DOI":"10.1186\/1471-2180-11-234"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"2795","DOI":"10.1099\/vir.0.19201-0","article-title":"Association of Japanese encephalitis virus NS3 protein with microtubules and tumour susceptibility gene 101 (TSG101) protein","volume":"84","author":"Chiou","year":"2003","journal-title":"J. Gen. Virol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/BF01311042","article-title":"Flavivirus infection: Essential ultrastructural changes and association of Kunjin virus NS3 protein with microtubules","volume":"106","author":"Ng","year":"1989","journal-title":"Arch. Virol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/12\/3335\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:36:50Z","timestamp":1760168210000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/12\/3335"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,27]]},"references-count":93,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["cells10123335"],"URL":"https:\/\/doi.org\/10.3390\/cells10123335","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,27]]}}}