title: Human Endometrial Stromal Cells Are Highly Permissive To Productive Infection by Zika Virus.
abstract: 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 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 together 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 ZIKV reaching them, either via the uterine vasculature in the viremic phase of the infection or by sexual viral transmission, and a potential source of virus spreading to placental trophoblasts during pregnancy.
authors.affiliation: Viral Pathogens and Biosafety Unit, Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Isabel
authors.initials: I
authors.lastname: Pagani
authors.affiliation: Viral Pathogens and Biosafety Unit, Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Ghezzi
authors.affiliation: Reproductive Sciences Laboratory, Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Adele
authors.initials: A
authors.lastname: Ulisse
authors.affiliation: Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Alicia
authors.initials: A
authors.lastname: Rubio
authors.affiliation: Viral Pathogens and Biosafety Unit, Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Turrini
authors.affiliation: Obstetrics and Gynecology Unit, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Garavaglia
authors.affiliation: Obstetrics and Gynecology Unit, San Raffaele Scientific Institute, Milan, Italy.|Vita-Salute San Raffaele University School of Medicine, Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Candiani
authors.affiliation: National Institute for Infectious Diseases "Lazzaro Spallanzani", Rome, Italy.
authors.forename: Concetta
authors.initials: C
authors.lastname: Castilletti
authors.affiliation: National Institute for Infectious Diseases "Lazzaro Spallanzani", Rome, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Ippolito
authors.affiliation: Vita-Salute San Raffaele University School of Medicine, Milan, Italy.|AIDS Immunopathogenesis Unit, Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Poli
authors.affiliation: National Research Council (CNR), Institute of Neuroscience, Milan, Italy.
authors.forename: Vania
authors.initials: V
authors.lastname: Broccoli
authors.affiliation: Reproductive Sciences Laboratory, Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Panina-Bordignon
authors.affiliation: Viral Pathogens and Biosafety Unit, Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Vicenzi
mesh_terms: D000328:Adult; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D004717:Endometrium / Q000166:cytology / Q000821:virology*; D005260:Female; D015870:Gene Expression; D054884:Host-Pathogen Interactions / Q000235:genetics; D006801:Humans; D016899:Interferon-beta / Q000235:genetics / Q000378:metabolism; D017154:Stromal Cells / Q000821:virology*; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication / Q000235:genetics / Q000502:physiology*; D000071244:Zika Virus / Q000235:genetics / Q000502:physiology*; D000071243:Zika Virus Infection / Q000235:genetics / Q000378:metabolism / Q000821:virology
chemical_list: D014759:Viral Envelope Proteins; D016899:Interferon-beta