{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T11:19:48Z","timestamp":1788347988970,"version":"build-2803163510"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,5,11]],"date-time":"2023-05-11T00:00:00Z","timestamp":1683763200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>Chikungunya virus (CHIKV) is an arthropod-borne virus recently associated with large outbreaks in many parts of the world. Infection is typically manifested as a febrile and self-limited illness, characterized by joint pain and myalgia, albeit severe neurological manifestations are also reported. Although CHIKV is not recognized as a truly neurotropic virus, neurons, astrocytes, and oligodendrocytes are susceptible to infection <jats:italic>in vitro<\/jats:italic>. Here we employed a model of 3D cell culture to obtain neurospheres from ATRA\/BNDF differentiated human neuroblastoma cells. We demonstrate that CHIKV is able to establish a productive infection, resulting in ultrastructural changes in cell morphology and impaired neuronal differentiation. Ultrastructural analysis of neurospheres infected with CHIKV during neuronal differentiation revealed diminished neuron dendrite formation, accumulation of viral particles associated with the plasma membrane, numerous cell vacuoles, and swollen mitochondria. Apoptotic cells were significantly increased at 72\u2009h post-infection. Compared to Zika virus, a well-characterized neurotropic arbovirus, CHIKV infection resulted in a more discrete, albeit detectable upregulation of IL-6 levels. Finally, we found that CHIKV infection resulted in an altered profile expression, mainly downregulation, of a group of transcription factors named Hox genes. Altogether our findings highlight important features of CHIKV in the CNS, as well as the feasibility of neurospheres as robust experimental models that can support further studies for novel pharmacological interventions.<\/jats:p>","DOI":"10.3389\/fmicb.2023.1152480","type":"journal-article","created":{"date-parts":[[2023,5,12]],"date-time":"2023-05-12T07:02:55Z","timestamp":1683874975000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Chikungunya virus infection induces ultrastructural changes and impaired neuronal differentiation of human neurospheres"],"prefix":"10.3389","volume":"14","author":[{"given":"Tha\u00edse Yasmine Vasconcelos","family":"de Lima Cavalcanti","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa de Almeida Neves","family":"Azevedo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morganna Costa","family":"Lima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karina Lidiane Alc\u00e2ntara","family":"Saraiva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael Freitas Oliveira","family":"Franca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,5,11]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"969","DOI":"10.3390\/v14050969","article-title":"A review on chikungunya virus epidemiology, pathogenesis and current vaccine development","volume":"14","author":"de Lima Cavalcanti","year":"2022","journal-title":"Viruses"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"e60","DOI":"10.1371\/journal.pmed.0050060","article-title":"Multidisciplinary prospective study of mother-to-child chikungunya virus infections on the island of La Reunion","volume":"5","author":"Gerardin","year":"2008","journal-title":"PLoS Med"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"826","DOI":"10.1016\/S1474-4422(20)30232-5","article-title":"Neurological disease in adults with Zika and chikungunya virus infection in Northeast Brazil: a prospective observational study","volume":"19","author":"Brito Ferreira","year":"2020","journal-title":"Lancet Neurol."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"e29","DOI":"10.1371\/journal.ppat.0040029","article-title":"A mouse model for chikungunya: young age and inefficient type-I interferon signaling are risk factors for severe disease","volume":"4","author":"Couderc","year":"2008","journal-title":"PLoS Pathog."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"e75854","DOI":"10.1371\/journal.pone.0075854","article-title":"Induction of cytopathogenicity in human glioblastoma cells by chikungunya virus","volume":"8","author":"Abraham","year":"2013","journal-title":"PLoS One"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1099\/0022-1317-23-3-271","article-title":"Isolation and persistence of chikungunya virus in cultures of mouse brain cells","volume":"23","author":"Precious","year":"1974","journal-title":"J. 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