Experimental Infection of Pregnant Female Sheep with Zika Virus During Early Gestation

Erika R. Schwarz, Malgorzata A. Pozor, Ruiyu Pu, Kelli L. Barr, Sarah E. Beachboard, Nigel J Maclachlan, Dhani Prakoso, Maureen T. Long

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Zika virus (ZIKV) is a vertically and sexually transmissible virus resulting in severe congenital malformation. The goal of this study was to develop an ovine model of ZIKV infection. Between 28-35 days gestation (DG), four pregnant animals were infected with two doses of 6 × 106 PFU of ZIKV; four control animals received PBS. Animals were evaluated for 45 days (D) post-infection (PI) and necropsies were performed. Viral RNA was detected in infected ewe peripheral blood mononuclear cells (PBMC) during the first week PI; however, all fluids and tissues were negative upon culture. Anti-ZIKV IgM (1:400) and neutralizing antibodies were detected in all infected animals. Clinical disease, virus, or ZIKV antibodies were not detected in control ewes. After two weeks PI, fetal loss occurred in two infected animals, and at necropsy, three infected animals had placental petechiation and ecchymosis and one had hydramnion. Fetal morphometrics revealed smaller cranial circumference to crown-rump length ratios (p < 0.001) and relative brain weights (p = 0.038) in fetuses of infected animals compared with control fetuses. Immunophenotyping indicated an increase in B cells (p = 0.012) in infected sheep. Additionally, in vitro experiments using both adult and fetal cell lines demonstrated that ovine cells are highly permissive to ZIKV infection. In conclusion, ZIKV infection of pregnant sheep results in a change in fetal growth and gestational outcomes.

Original languageEnglish (US)
JournalViruses
Volume11
Issue number9
DOIs
StatePublished - Aug 29 2019

Keywords

  • animal model
  • ovine
  • pregnancy
  • sheep
  • vertical transmission
  • Zika Virus
  • ZIKV

ASJC Scopus subject areas

  • Infectious Diseases
  • Virology

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    Schwarz, E. R., Pozor, M. A., Pu, R., Barr, K. L., Beachboard, S. E., Maclachlan, N. J., Prakoso, D., & Long, M. T. (2019). Experimental Infection of Pregnant Female Sheep with Zika Virus During Early Gestation. Viruses, 11(9). https://doi.org/10.3390/v11090795