Ocular and uteroplacental pathology in a macaque pregnancy with congenital Zika virus infection

Emma L. Mohr, Lindsey N. Block, Christina M. Newman, Laurel M. Stewart, Michelle Koenig, Matthew Semler, Meghan E. Breitbach, Leandro B.C. Teixeira, Xiankun Zeng, Andrea M. Weiler, Gabrielle L. Barry, Troy H. Thoong, Gregory J. Wiepz, Dawn M. Dudley, Heather A. Simmons, Andres Mejia, Terry K. Morgan, M. Shahriar Salamat, Sarah Kohn, Kathleen M. AntonyMatthew T. Aliota, Mariel S. Mohns, Jennifer M. Hayes, Nancy Schultz-Darken, Michele L. Schotzko, Eric Peterson, Saverio Capuano, Jorge E. Osorio, Shelby L. O’Connor, Thomas C. Friedrich, David H. O’Connor, Thaddeus G. Golos

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

Congenital Zika virus (ZIKV) infection impacts fetal development and pregnancy outcomes. We infected a pregnant rhesus macaque with a Puerto Rican ZIKV isolate in the first trimester. The pregnancy was complicated by preterm premature rupture of membranes (PPROM), intraamniotic bacterial infection and fetal demise 49 days post infection (gestational day 95). Significant pathology at the maternal-fetal interface included acute chorioamnionitis, placental infarcts, and leukocytoclastic vasculitis of the myometrial radial arteries. ZIKV RNA was disseminated throughout fetal tissues and maternal immune system tissues at necropsy, as assessed by quantitative RT-PCR for viral RNA. Replicating ZIKV was identified in fetal tissues, maternal uterus, and maternal spleen by fluorescent in situ hybridization for viral replication intermediates. Fetal ocular pathology included a choroidal coloboma, suspected anterior segment dysgenesis, and a dysplastic retina. This is the first report of ocular pathology and prolonged viral replication in both maternal and fetal tissues following congenital ZIKV infection in a rhesus macaque. PPROM followed by fetal demise and severe pathology of the visual system have not been described in macaque congenital ZIKV infection previously. While this case of ZIKV infection during pregnancy was complicated by bacterial infection with PPROM, the role of ZIKV on this outcome cannot be precisely defined, and further nonhuman primate studies will determine if increased risk for PPROM or other adverse pregnancy outcomes are associated with congenital ZIKV infection.

Original languageEnglish (US)
Article numbere0190617
JournalPloS one
Volume13
Issue number1
DOIs
StatePublished - Jan 2018

Bibliographical note

Funding Information:
This study was supported by the National Institutes of Health (R21 HD091163-01, R01 AI116382-01A1S1, P51 OD011106, T32 AI55397) and the Pediatric Infectious Diseases Society. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Opinions, interpretations, conclusions, and recommendations are those of the author (X. Zeng) and are not necessarily endorsed by the U.S. Army.

Publisher Copyright:
This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

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