Zika virus infection of first trimester trophoblast cells affects cell migration, metabolism and immune homeostasis control

DAIANA VOTA; FLORENCIA TORTI; DANIEL PAPARINI; FEDERICO GIOVANNONI; FATIMA MERECH; VANESA HAUK; GUILLERMINA CALO; ROSANNA RAMHORST; CYBELE GARCIA; CLAUDIA PEREZ LEIROS

JOURNAL OF CELLULAR PHYSIOLOGY

WILEY-LISS, DIV JOHN WILEY & SONS INC

Lugar: New York; Año: 2020

0021-9541

Zika virus (ZIKV) re-emerged after circulating almost undetected for many years and the lastspread in 2015 was the major outbreak reported. ZIKV infection was associated with congenitalfetal growth anomalies such as microcephaly, brain calcifications and low birth weight related tofetal growth restriction. In this study, we investigated the effect of ZIKV infection on firsttrimester trophoblast cell function and metabolism. We also studied the interaction oftrophoblast cells with decidual immune populations. Results presented here demonstrate thatZIKV infection triggered a strong antiviral response in first trimester cytotrophoblast-derivedcells, impaired cell migration, increased glucose uptake and GLUT3 expression and reducedBrain Derived Neurotrophic Factor (BDNF) expression. ZIKV infection also conditionedtrophoblast cells to favor a tolerogenic response since an increased recruitment of CD14+monocytes bearing an anti-inflammatory profile, increased CD4+ T cells and NK CD56Dim andNK CD56Bright populations and an increment in the population CD4+FOXP3+IL-10+ cells wasobserved. Interestingly, when ZIKV infection of trophoblast cells occurred in the presence of thevasoactive intestinal peptide (VIP) there was lower detection of viral RNA and reduced TLR-3and viperin mRNA expression, along with reduced CD56Dim cells trafficking to trophoblastconditioned media. The effects of ZIKV infection on trophoblast cell function and immune-trophoblast interaction shown here could contribute to defective placentation and ZIKVpersistence at the fetal-maternal interface. The inhibitory effect of VIP on ZIKV infection oftrophoblast cells highlights its potential as a candidate molecule to interfere ZIKV infectionduring early pregnancy.