RT Journal Article
SR Electronic
T1 Human Endometrial Stromal Cells Are Highly Permissive To Productive Infection by Zika Virus
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 077305
DO 10.1101/077305
A1 Isabel Pagani
A1 Silvia Ghezzi
A1 Adele Ulisse
A1 Alicia Rubio
A1 Filippo Turrini
A1 Elisabetta Garavaglia
A1 Massimo Candiani
A1 Concetta Castilletti
A1 Giuseppe Ippolito
A1 Guido Poli
A1 Vania Broccoli
A1 Paola Panina-Bordignon
A1 Elisa Vicenzi
YR 2016
UL http://biorxiv.org/content/early/2016/09/27/077305.abstract
AB Zika virus (ZIKV) is a recently re-emerged flavivirus transmitted to humans by mosquito bites but also from mother to fetus and by sexual intercourse. We here show for the first time that primary human endometrial stromal cells (HESC) are highly permissive to ZIKV infection and support its in vitro replication. ZIKV envelope expression was detected in the endoplasmic reticulum whereas double-stranded viral RNA colocalized with vimentin filaments to the perinuclear region. ZIKV productive infection also occurred in the human T-HESC cell line with the induction of interferon-β (IFN-β) and of IFN-stimulated genes. Notably, in vitro decidualization of T-HESC with cyclic AMP and progesterone upregulated the cell surface expression of the ZIKV entry co-receptor AXL and boosted ZIKV replication by ca. 100-fold. Thus, endometrial stromal cells, particularly if decidualized, likely represent a crucial cell target of sexual virus transmission and a relevant source of ZIKV spreading to placental trophoblasts during pregnancy.AUTHOR SUMMARY Infection by Zika virus (ZIKV), a flavivirus transmitted to humans by mosquito bites, has recently emerged as an important cause of neurological lesions in the fetal brain as women who become infected by ZIKV during pregnancy can transmit the virus to their fetus. In addition, routes of ZIKV transmission independent of mosquito bites have been also identified and include sexual transmission from both infected men and women to their partners, an aspect bearing great societal implications for ZIKV spread. These observations highlight the importance of the female reproductive tract in the establishment and/or spreading of the infection. In this regard, the endometrium is a highly dynamic tissue undergoing major histological changes during the menstrual cycle under the coordinated action of sexual hormones. In particular, progesterone drives the differentiation of human endometrial stromal cells towards decidualization, a process that is critical for fetal trophoblast invasion and placenta formation. We here report for the first time that both primary and immortalized human endometrial stromal cells are highly permissive to ZIKV infection and replication, particularly when in vitro decidualized by progesterone, suggesting that these cells could significantly contribute to vertical ZIKV transmission in utero during pregnancy but also to horizontal transmission by the sexual route.