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Cytotrophoblast cells are selectively permissive and favor Zika virus, but no other related flavivirus, invasion to the placental stroma

Viettri, M. I.; Caraballo, G. I.; Sanchez, M. E.; Espejel-Nunez, A.; Betanzos, A.; Ortiz-Navarrete, V.; Estrada, G.; Nava, P.; Ludert, J. E.

2023-01-21 microbiology
10.1101/2023.01.20.524913 bioRxiv
Show abstract

BACKGROUNDZika virus (ZIKV) is highly teratogenic, in contrast with dengue virus (DENV) or the yellow fever virus vaccine (YFV-17D). The mechanisms employed by ZIKV to cross the placenta need to be elucidated. METHODSParallel infections with ZIKV, DENV and YFV-17D were compared in terms of efficiency, activation of mTOR pathways and cytokine secretion profile in human cytotrophoblastic HTR8 cells (CTB), and monocytic U937 cells, differentiated to M2 macrophages (M2-MO). RESULTSIn CTB, ZIKV replication was significantly more efficient than DENV or YFV-17D. In M2-MO, ZIKV replication continued to be more efficient, although differences between strains were reduced. Significantly greater activation of Phospho-S6r and Phospho-AKT/Ser473 fractions in CTB infected with ZIKV than with DENV or YFV-17D, was observed. CTB treated with the mTOR inhibitors rapamycin or AZD8055, showed a 20-fold-reduction in ZIKV yield, versus 5 and 3.5-fold for DENV and YFV-17D, respectively. Finally, we detected that ZIKV infection, but not DENV or YFV-17D, efficiently inhibited the interferon response of CTB cells. CONCLUSIONSThese results suggest that CTB cells are permissive and act favoring ZIKV entry into the placental stroma, over DENV and YFV-17D and that the mTOR complex is a switch that enhances the replication of ZIKV in CTB cells.

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