title: Zika Virus Infects Human Placental Macrophages.
abstract: The recent Zika virus (ZIKV) outbreak in Brazil has been directly linked to increased cases of microcephaly in newborns. Current evidence indicates that ZIKV is transmitted vertically from mother to fetus. However, the mechanism of intrauterine transmission and the cell types involved remain unknown. We demonstrate that the contemporary ZIKV strain PRVABC59 (PR 2015) infects and replicates in primary human placental macrophages, called Hofbauer cells, and to a lesser extent in cytotrophoblasts, isolated from villous tissue of full-term placentae. Viral replication coincides with induction of type I interferon (IFN), pro-inflammatory cytokines, and antiviral gene expression, but with minimal cell death. Our results suggest a mechanism for intrauterine transmission in which ZIKV gains access to the fetal compartment by directly infecting placental cells and disrupting the placental barrier.
authors.affiliation: Department of Pediatrics, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, GA 30322, USA; Emory Vaccine Center, Yerkes National Primate Research Center, Atlanta, GA 30329, USA.
authors.forename: Kendra M
authors.initials: KM
authors.lastname: Quicke
authors.affiliation: Department of Pediatrics, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, GA 30322, USA; Emory Vaccine Center, Yerkes National Primate Research Center, Atlanta, GA 30329, USA.
authors.forename: James R
authors.initials: JR
authors.lastname: Bowen
authors.affiliation: Department of Pediatrics, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Erica L
authors.initials: EL
authors.lastname: Johnson
authors.affiliation: Department of Pediatrics, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, GA 30322, USA; Emory Vaccine Center, Yerkes National Primate Research Center, Atlanta, GA 30329, USA.
authors.forename: Circe E
authors.initials: CE
authors.lastname: McDonald
authors.affiliation: Emory Vaccine Center, Yerkes National Primate Research Center, Atlanta, GA 30329, USA; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Huailiang
authors.initials: H
authors.lastname: Ma
authors.affiliation: Department of Pediatrics, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, GA 30322, USA; Emory Vaccine Center, Yerkes National Primate Research Center, Atlanta, GA 30329, USA.
authors.forename: Justin T
authors.initials: JT
authors.lastname: O'Neal
authors.affiliation: Department of Gynecology and Obstetrics, Division of Maternal Fetal Medicine and Reproductive Infectious Diseases, Emory University School of Medicine, Atlanta, GA 30329, USA.
authors.forename: Augustine
authors.initials: A
authors.lastname: Rajakumar
authors.affiliation: Department of Pediatrics, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, GA 30322, USA; Emory Vaccine Center, Yerkes National Primate Research Center, Atlanta, GA 30329, USA.
authors.forename: Jens
authors.initials: J
authors.lastname: Wrammert
authors.affiliation: Department of Gynecology and Obstetrics, Division of Maternal Fetal Medicine and Reproductive Infectious Diseases, Emory University School of Medicine, Atlanta, GA 30329, USA.
authors.forename: Bassam H
authors.initials: BH
authors.lastname: Rimawi
authors.affiliation: Emory Vaccine Center, Yerkes National Primate Research Center, Atlanta, GA 30329, USA; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Bali
authors.initials: B
authors.lastname: Pulendran
authors.affiliation: Department of Pediatrics, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, GA 30322, USA; Center for AIDS Research, Laboratory of Biochemical Pharmacology, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Raymond F
authors.initials: RF
authors.lastname: Schinazi
authors.affiliation: Department of Pediatrics, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Rana
authors.initials: R
authors.lastname: Chakraborty
authors.affiliation: Department of Pediatrics, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, GA 30322, USA; Emory Vaccine Center, Yerkes National Primate Research Center, Atlanta, GA 30329, USA. Electronic address: msuthar@emory.edu.
authors.forename: Mehul S
authors.initials: MS
authors.lastname: Suthar
mesh_terms: D016923:Cell Death; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D008264:Macrophages / Q000821:virology*; D010920:Placenta / Q000166:cytology*; D011247:Pregnancy; D014327:Trophoblasts / Q000821:virology; D056189:Viral Tropism; D014779:Virus Replication; D000071244:Zika Virus / Q000502:physiology*
chemical_list: D016207:Cytokines