title: Viral infection, proliferation, and hyperplasia of Hofbauer cells and absence of inflammation characterize the placental pathology of fetuses with congenital Zika virus infection.
abstract: OBJECTIVE
  Attention is increasingly focused on the potential mechanism(s) for Zika virus infection to be transmitted from an infected mother to her fetus. This communication addresses current evidence for the role of the placenta in vertical transmission of the Zika virus.
  
  
  METHODS
  Placentas from second and third trimester fetuses with confirmed intrauterine Zika virus infection were examined with routine staining to determine the spectrum of pathologic changes. In addition, immunohistochemical staining for macrophages and nuclear proliferation antigens was performed. Viral localization was identified using RNA hybridization. These observations were combined with the recent published results of placental pathology to increase the strength of the pathology data. Results were correlated with published data from experimental studies of Zika virus infection in placental cells and chorionic villous explants.
  
  
  RESULTS
  Placentas from fetuses with congenital Zika virus infection are concordant in not having viral-induced placental inflammation. Special stains reveal proliferation and prominent hyperplasia of placental stromal macrophages, termed Hofbauer cells, in the chorionic villi of infected placentas. Zika virus infection is present in Hofbauer cells from second and third trimester placentas. Experimental studies and placentae from infected fetuses reveal that the spectrum of placental cell types infected with the Zika virus is broader during the first trimester than later in gestation.
  
  
  CONCLUSIONS
  Inflammatory abnormalities of the placenta are not a component of vertical transmission of the Zika virus. The major placental response in second and third trimester transplacental Zika virus infection is proliferation and hyperplasia of Hofbauer cells, which also demonstrate viral infection.
authors.affiliation: Department of Pathology, Medical College of Georgia, Augusta University, Augusta, Georgia. davidalanschwartz@gmail.com.
authors.forename: David A
authors.identifier: http://orcid.org/0000-0002-7486-8545
authors.initials: DA
authors.lastname: Schwartz
mesh_terms: D049109:Cell Proliferation; D002824:Chorionic Villi / Q000473:pathology; D005260:Female; D005333:Fetus / Q000473:pathology; D006801:Humans; D006965:Hyperplasia / Q000473:pathology*; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical; D007249:Inflammation / Q000473:pathology; D008264:Macrophages / Q000473:pathology; D010920:Placenta / Q000473:pathology* / Q000821:virology; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000473:pathology / Q000821:virology*; D011261:Pregnancy Trimester, First; D011263:Pregnancy Trimester, Third; D000071243:Zika Virus Infection / Q000150:complications* / Q000635:transmission
keywords: Infection; Microcephaly; Pathology; Placenta; Virus; Zika