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We investigated the mechanisms of skeletal muscle susceptibility to ZIKV using an <jats:italic>in vitro<\/jats:italic> model of human skeletal muscle myogenesis, in which myoblasts differentiate into myotubes. Myoblasts were permissive to ZIKV infection, generating productive viral particles, while myotubes controlled ZIKV replication. To investigate the underlying mechanisms, we used gene expression profiling. First, we assessed gene changes in myotubes compared with myoblasts in the model without infection. As expected, we observed an increase in genes and pathways related to the contractile muscle system in the myotubes, a reduction in processes linked to proliferation, migration and cytokine production, among others, confirming the myogenic capacity of our system in vitro. A comparison between non-infected and infected myoblasts revealed more than 500 differentially expressed genes (DEGs). In contrast, infected myotubes showed almost 2,000 DEGs, among which we detected genes and pathways highly or exclusively expressed in myotubes, including those related to antiviral and innate immune responses. Such gene modulation could explain our findings showing that ZIKV also invades myotubes but does not replicate in these differentiated cells. In conclusion, we showed that ZIKV largely (but differentially) disrupts gene expression in human myoblasts and myotubes. Identifying genes involved in myotube resistance can shed light on potential antiviral mechanisms against ZIKV infection.<\/jats:p>","DOI":"10.1371\/journal.pntd.0010166","type":"journal-article","created":{"date-parts":[[2022,2,16]],"date-time":"2022-02-16T18:46:43Z","timestamp":1645037203000},"page":"e0010166","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":8,"title":["Zika virus disrupts gene expression in human myoblasts and myotubes: Relationship with susceptibility to infection"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7171-9977","authenticated-orcid":true,"given":"Ingo","family":"Riederer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3697-1506","authenticated-orcid":true,"given":"Daniella Ar\u00eaas","family":"Mendes-da-Cruz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guilherme Cordenonsi","family":"da Fonseca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariela Natacha","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Otavio","family":"Brustolini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e1ssia","family":"Rocha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guilherme","family":"Loss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseane Biso","family":"de Carvalho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1042-2990","authenticated-orcid":true,"given":"Mariane Talon","family":"Menezes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lidiane Menezes Souza","family":"Raphael","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5724-6106","authenticated-orcid":true,"given":"Alexandra","family":"Gerber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9899-3386","authenticated-orcid":true,"given":"Myrna Cristina","family":"Bonaldo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gillian","family":"Butler-Browne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3809-4033","authenticated-orcid":true,"given":"Vincent","family":"Mouly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6753-3480","authenticated-orcid":true,"given":"Vinicius","family":"Cotta-de-Almeida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5802-3120","authenticated-orcid":true,"given":"Wilson","family":"Savino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4632-2086","authenticated-orcid":true,"given":"Ana Tereza","family":"Ribeiro de Vasconcelos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,2,16]]},"reference":[{"issue":"6","key":"pntd.0010166.ref001","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1001\/jamadermatol.2016.1635","article-title":"Zika virus.","volume":"152","author":"DJG Didier Musso","year":"2016","journal-title":"JAMA Dermatology"},{"issue":"1","key":"pntd.0010166.ref002","first-page":"1","article-title":"Zika Virus Infection as a Cause of Congenital Brain Abnormalities and Guillain\u2013Barr\u00e9 Syndrome","volume":"14","author":"F Krauer","year":"2017","journal-title":"Systematic Review. 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