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Severe dengue is correlated with high viraemia and cytokine storm, such as high levels of transforming growth factor\u2010\u03b21 (TGF\u2010\u03b21) in the patient's serum. Here, the TGF\u2010\u03b21 signaling was investigated in the context of in vitro viral clearance. Macrophages were infected with DENV\u20102 at MOI 5 and treated with the TGF\u2010\u03b2 receptor 1 and 2 inhibitor, GW788388. TGF\u2010\u03b21 expression, signal transduction and viral load were evaluated 48\u2009h after DENV\u20102 infection by enzyme\u2010linked immunoassay, immunofluorescence, and RT\u2010qPCR assays. Total TGF\u2010\u03b21 level was reduced in 15% after DENV\u20102 infection, but the secretion of its biologically active form increased threefold during infection, which was followed by the phosphorylation of Smad2 protein. Phosphorylation of Smad2 was reduced by treatment with GW788388 and it was correlated with reduced cytokine production. Importantly, treatment led to a dose\u2010dependent reduction in viral load, ranging from 6.6\u2009\u00d7\u200910<jats:sup>5<\/jats:sup> RNA copies\/ml in untreated cultures to 2.3\u2009\u00d7\u200910<jats:sup>3<\/jats:sup> RNA copies\/ml in cultures treated with 2\u2009ng\/ml of GW788388. The anti\u2010TGF\u2010\u03b21 antibody treatment also induced a significant reduction in viral load to 1.6\u2009\u00d7\u200910<jats:sup>3<\/jats:sup> RNA copies\/ml. On the other hand, the addition of recombinant TGF\u2010\u03b21 in infected cultures promoted an increase in viral load to 7.0\u2009\u00d7\u200910<jats:sup>6<\/jats:sup> RNA copies\/ml. These results support that TGF\u2010\u03b21 plays a significant role in DENV\u20102 replication into macrophages and suggest that targeting TGF\u2010\u03b21 may represent an alternative therapeutic strategy to be explored in dengue infection.<\/jats:p>","DOI":"10.1002\/jmv.27879","type":"journal-article","created":{"date-parts":[[2022,5,21]],"date-time":"2022-05-21T03:04:21Z","timestamp":1653102261000},"page":"4359-4368","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Suppression of TGF\u2010\u03b2\/Smad2 signaling by GW788388 enhances DENV\u20102 clearance in macrophages"],"prefix":"10.1002","volume":"94","author":[{"given":"Gabrielly Sbano","family":"Teixeira","sequence":"first","affiliation":[{"name":"Instituto Oswaldo Cruz, Funda\u00e7\u00e3o Oswaldo Cruz Laborat\u00f3rio de Morfologia e Morfog\u00eanese Viral  Rio de Janeiro Rio de Janeiro Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Audrien Alves","family":"Andrade","sequence":"additional","affiliation":[{"name":"Instituto Oswaldo Cruz, Funda\u00e7\u00e3o Oswaldo Cruz Laborat\u00f3rio de Virologia Molecular  Rio de Janeiro Rio de Janeiro Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauana Ribas","family":"Torres","sequence":"additional","affiliation":[{"name":"Instituto Oswaldo Cruz, Funda\u00e7\u00e3o Oswaldo Cruz Laborat\u00f3rio de Virologia Molecular  Rio de Janeiro Rio de Janeiro Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dinair","family":"Couto\u2010Lima","sequence":"additional","affiliation":[{"name":"Instituto Oswaldo Cruz, Funda\u00e7\u00e3o Oswaldo Cruz Laborat\u00f3rio de Mosquitos Transmissores de Hematozo\u00e1rio  Rio de Janeiro Rio de Janeiro Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Otacilio C.","family":"Moreira","sequence":"additional","affiliation":[{"name":"Instituto Oswaldo Cruz, Funda\u00e7\u00e3o Oswaldo Cruz Plataforma de PCR em Tempo Real RPT09A, Laborat\u00f3rio de Biologia Molecular e Doen\u00e7as End\u00eamicas  Rio de Janeiro Rio de Janeiro Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rayane","family":"Abreu","sequence":"additional","affiliation":[{"name":"Instituto Oswaldo Cruz, Funda\u00e7\u00e3o Oswaldo Cruz Laborat\u00f3rio de Gen\u00f4mica Funcional e Bioinform\u00e1tica  Rio de Janeiro Rio de Janeiro Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana Caldas","family":"Waghabi","sequence":"additional","affiliation":[{"name":"Instituto Oswaldo Cruz, Funda\u00e7\u00e3o Oswaldo Cruz Laborat\u00f3rio de Gen\u00f4mica Funcional e Bioinform\u00e1tica  Rio de Janeiro Rio de Janeiro Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6512-6542","authenticated-orcid":false,"given":"Elen Mello","family":"de Souza","sequence":"additional","affiliation":[{"name":"Instituto Oswaldo Cruz, Funda\u00e7\u00e3o Oswaldo Cruz Laborat\u00f3rio de Morfologia e Morfog\u00eanese Viral  Rio de Janeiro Rio de Janeiro Brazil"},{"name":"Instituto Oswaldo Cruz, Funda\u00e7\u00e3o Oswaldo Cruz Laborat\u00f3rio de Virologia Molecular  Rio de Janeiro Rio de Janeiro Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,6,2]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/v12080829"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-016-0907-2"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)32560-1"},{"issue":"7","key":"e_1_2_9_5_1","first-page":"1","article-title":"Monitoramento dos casos de arboviroses urbanas causados por v\u00edrus transmitidos pelo mosquito Aedes (dengue, chikungunya e zika), semanas epidemiol\u00f3gicas 1 a 7, 2022","volume":"53","author":"SVS \u2010 Secretaria de Vigil\u00e2ncia em Sa\u00fade Sanit\u00e1ria","year":"2022","journal-title":"Minist\u00e9rio da Sa\u00fade"},{"issue":"41","key":"e_1_2_9_6_1","first-page":"1","article-title":"Monitoramento dos casos de arboviroses urbanas causados por v\u00edrus transmitidos pelo mosquito Aedes (dengue, chikungunya e zika), semanas epidemiol\u00f3gicas 1 a 44, 2021","volume":"52","author":"SVS \u2010 Secretaria de Vigil\u00e2ncia em Sa\u00fade Sanit\u00e1ria","year":"2021","journal-title":"Minist\u00e9rio da Sa\u00fade"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiw341"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1586\/14760584.2016.1115727"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1586\/14760584.2016.1128328"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)61687-0"},{"key":"e_1_2_9_11_1","unstructured":"WHO(2009) Dengue: guidelines for diagnosis treatment prevention and control; 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