title: Primary Human Placental Trophoblasts are Permissive for Zika Virus (ZIKV) Replication.
abstract: Zika virus (ZIKV) is an emerging mosquito-borne (Aedes genus) arbovirus of the Flaviviridae family. Although ZIKV has been predominately associated with a mild or asymptomatic dengue-like disease, its appearance in the Americas has been accompanied by a multi-fold increase in reported incidence of fetal microcephaly and brain malformations. The source and mode of vertical transmission from mother to fetus is presumptively transplacental, although a causal link explaining the interval delay between maternal symptoms and observed fetal malformations following infection has been missing. In this study, we show that primary human placental trophoblasts from non-exposed donors (n = 20) can be infected by primary passage ZIKV-FLR isolate, and uniquely allowed for ZIKV viral RNA replication when compared to dengue virus (DENV). Consistent with their being permissive for ZIKV infection, primary trophoblasts expressed multiple putative ZIKV cell entry receptors, and cellular function and differentiation were preserved. These findings suggest that ZIKV-FLR strain can replicate in human placental trophoblasts without host cell destruction, thereby serving as a likely permissive reservoir and portal of fetal transmission with risk of latent microcephaly and malformations.
authors.affiliation: Departments of Obstetrics &Gynecology, Division of Maternal-Fetal Medicine at Baylor College of Medicine &Texas Children's Hospital, Houston, TX, USA.|Department of Molecular &Human Genetics at Baylor College of Medicine, Houston, TX, USA.|Department of Molecular &Cellular Biology at Baylor College of Medicine, Houston, TX, USA.|National School for Tropical Medicine at Baylor College of Medicine, Houston, TX, USA.
authors.forename: Kjersti M
authors.initials: KM
authors.lastname: Aagaard
authors.affiliation: Department of Molecular Virology &Microbiology, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Anismrita
authors.initials: A
authors.lastname: Lahon
authors.affiliation: Departments of Obstetrics &Gynecology, Division of Maternal-Fetal Medicine at Baylor College of Medicine &Texas Children's Hospital, Houston, TX, USA.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Suter
authors.affiliation: Department of Molecular Virology &Microbiology, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Ravi P
authors.initials: RP
authors.lastname: Arya
authors.affiliation: Departments of Obstetrics &Gynecology, Division of Maternal-Fetal Medicine at Baylor College of Medicine &Texas Children's Hospital, Houston, TX, USA.
authors.forename: Maxim D
authors.initials: MD
authors.lastname: Seferovic
authors.affiliation: Department of Molecular Virology &Microbiology, Baylor College of Medicine, Houston, TX, USA.|Integrative Molecular and Biological Science Program, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Megan B
authors.initials: MB
authors.lastname: Vogt
authors.affiliation: Departments of Obstetrics &Gynecology, Division of Maternal-Fetal Medicine at Baylor College of Medicine &Texas Children's Hospital, Houston, TX, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Hu
authors.affiliation: Department of Molecular &Cellular Biology at Baylor College of Medicine, Houston, TX, USA.
authors.forename: Fabio
authors.initials: F
authors.lastname: Stossi
authors.affiliation: Department of Molecular &Cellular Biology at Baylor College of Medicine, Houston, TX, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Mancini
authors.affiliation: Departments of Obstetrics &Gynecology, Division of Maternal-Fetal Medicine at Baylor College of Medicine &Texas Children's Hospital, Houston, TX, USA.|Department of Molecular &Human Genetics at Baylor College of Medicine, Houston, TX, USA.
authors.forename: R Alan
authors.initials: RA
authors.lastname: Harris
authors.affiliation: Departments of Obstetrics &Gynecology, Division of Maternal-Fetal Medicine at Baylor College of Medicine &Texas Children's Hospital, Houston, TX, USA.
authors.forename: Maike
authors.initials: M
authors.lastname: Kahr
authors.affiliation: Departments of Obstetrics &Gynecology, Division of Maternal-Fetal Medicine at Baylor College of Medicine &Texas Children's Hospital, Houston, TX, USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: Eppes
authors.affiliation: Departments of Obstetrics &Gynecology, Division of Maternal-Fetal Medicine at Baylor College of Medicine &Texas Children's Hospital, Houston, TX, USA.
authors.forename: Martha
authors.initials: M
authors.lastname: Rac
authors.affiliation: Departments of Obstetrics &Gynecology, Division of Maternal-Fetal Medicine at Baylor College of Medicine &Texas Children's Hospital, Houston, TX, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Belfort
authors.affiliation: Department of Pathology &Immunology, Baylor College of Medicine &Texas Children's Hospital, Houston, TX, USA.
authors.forename: Chun Shik
authors.initials: CS
authors.lastname: Park
authors.affiliation: Department of Pathology &Immunology, Baylor College of Medicine &Texas Children's Hospital, Houston, TX, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Lacorazza
authors.affiliation: Department of Molecular Virology &Microbiology, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Rico-Hesse
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D003715:Dengue / Q000473:pathology / Q000821:virology; D003716:Dengue Virus / Q000502:physiology; D005260:Female; D015726:Giant Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008024:Ligands; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D010802:Phylogeny; D010920:Placenta / Q000473:pathology*; D011247:Pregnancy; D012367:RNA, Viral / Q000378:metabolism; D011991:Receptors, Virus / Q000378:metabolism; D051193:Toll-Like Receptors / Q000378:metabolism; D014327:Trophoblasts / Q000821:virology*; D014779:Virus Replication / Q000502:physiology*; D000071244:Zika Virus / Q000502:physiology*; D000071243:Zika Virus Infection / Q000473:pathology / Q000821:virology
chemical_list: D008024:Ligands; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D012367:RNA, Viral; D011991:Receptors, Virus; D051193:Toll-Like Receptors