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ZIKV infection was associated with congenital fetal growth anomalies such as microcephaly, brain calcifications, and low birth weight related to fetal growth restriction. In this study, we investigated the effect of ZIKV infection on first trimester trophoblast cell function and metabolism. We also studied the interaction of trophoblast cells with decidual immune populations. Results presented here demonstrate that ZIKV infection triggered a strong antiviral response in first trimester cytotrophoblast\u2010derived cells, impaired cell migration, increased glucose uptake and GLUT3 expression, and reduced brain derived neurotrophic factor (BDNF) expression. ZIKV infection also conditioned trophoblast cells to favor a tolerogenic response since an increased recruitment of CD14+ monocytes bearing an anti\u2010inflammatory profile, increased CD4+ T cells and NK CD56<jats:sup>Dim<\/jats:sup> and NK CD56<jats:sup>Bright<\/jats:sup> populations and an increment in the population CD4+\u2009FOXP3+\u2009IL\u201010+ cells was observed. Interestingly, when ZIKV infection of trophoblast cells occurred in the presence of the vasoactive intestinal peptide (VIP) there was lower detection of viral RNA and reduced toll\u2010like receptor\u20103 and viperin messenger RNA expression, along with reduced CD56<jats:sup>Dim<\/jats:sup> cells trafficking to trophoblast conditioned media. The effects of ZIKV infection on trophoblast cell function and immune\u2010trophoblast interaction shown here could contribute to defective placentation and ZIKV persistence at the fetal\u2010maternal interface. The inhibitory effect of VIP on ZIKV infection of trophoblast cells highlights its potential as a candidate molecule to interfere ZIKV infection during early pregnancy.<\/jats:p>","DOI":"10.1002\/jcp.30203","type":"journal-article","created":{"date-parts":[[2020,12,11]],"date-time":"2020-12-11T07:02:56Z","timestamp":1607670176000},"page":"4913-4925","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Zika virus infection of first trimester trophoblast cells affects cell migration, metabolism and immune homeostasis control"],"prefix":"10.1002","volume":"236","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0418-2772","authenticated-orcid":false,"given":"Daiana","family":"Vota","sequence":"first","affiliation":[{"name":"Universidad de Buenos Aires (UBA). Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET). Instituto de Qu\u00edmica Biol\u00f3gica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN\u2010CONICET). Laboratorio de Inmunofarmacolog\u00eda. Facultad de Ciencias Exactas y Naturales (FCEN\u2010UBA)  Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Torti","sequence":"additional","affiliation":[{"name":"Universidad de Buenos Aires (UBA). Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET). Instituto de Qu\u00edmica Biol\u00f3gica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN\u2010CONICET). Laboratorio de Estrategias Antivrales. Facultad de Ciencias Exactas y Naturales (FCEN\u2010UBA)  Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Paparini","sequence":"additional","affiliation":[{"name":"Universidad de Buenos Aires (UBA). Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET). 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Instituto de Qu\u00edmica Biol\u00f3gica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN\u2010CONICET). Laboratorio de Inmunofarmacolog\u00eda. Facultad de Ciencias Exactas y Naturales (FCEN\u2010UBA)  Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanesa","family":"Hauk","sequence":"additional","affiliation":[{"name":"Universidad de Buenos Aires (UBA). Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET). Instituto de Qu\u00edmica Biol\u00f3gica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN\u2010CONICET). Laboratorio de Inmunofarmacolog\u00eda. Facultad de Ciencias Exactas y Naturales (FCEN\u2010UBA)  Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1413-3560","authenticated-orcid":false,"given":"Guillermina","family":"Calo","sequence":"additional","affiliation":[{"name":"Universidad de Buenos Aires (UBA). 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