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

• DOI: 10.1371/journal.pone.0190617
• Publication Date: 2018-01-30T18:39:51Z
• Authors: Emma L. Mohr; Lindsey N. Block; Christina M. Newman; Laurel M. Stewart; Michelle Koenig; Matthew Semler; Meghan E. Breitbach; Leandro B. C. Tei...; 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. Antony; Matthew 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
• Keywords: 0301 basic medicine; Zika Virus Infection; Science; Placenta; Q; Uterus; R; Zika Virus; Eye; Virus Replication; Macaca mulatta; 3. Good health; Disease Models, Animal; 03 medical and health sciences; Pregnancy; Medicine; Animals; RNA, Viral; Female; In Situ Hybridization, Fluorescence; Research Article

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.