Early Embryonic Loss Following Intravaginal Zika Virus Challenge in Rhesus Macaques

Christina M. Newman, Alice F. Tarantal, Michele L. Martinez, Heather A. Simmons, Terry K. Morgan, Xiankun Zeng, Jenna R. Rosinski, Mason I. Bliss, Ellie K. Bohm, Dawn M. Dudley, Matthew T. Aliota, Thomas C. Friedrich, Christopher J. Miller, David H. O’Connor

Research output: Contribution to journalArticlepeer-review

Abstract

Zika virus (ZIKV) is an arthropod-borne virus (arbovirus) and is primarily transmitted by Aedes species mosquitoes; however, ZIKV can also be sexually transmitted. During the initial epidemic and in places where ZIKV is now considered endemic, it is difficult to disentangle the risks and contributions of sexual versus vector-borne transmission to adverse pregnancy outcomes. To examine the potential impact of sexual transmission of ZIKV on pregnancy outcome, we challenged three rhesus macaques (Macaca mulatta) three times intravaginally with 1 x 107 PFU of a low passage, African lineage ZIKV isolate (ZIKV-DAK) in the first trimester (~30 days gestational age). Samples were collected from all animals initially on days 3 through 10 post challenge, followed by twice, and then once weekly sample collection; ultrasound examinations were performed every 3-4 days then weekly as pregnancies progressed. All three dams had ZIKV RNA detectable in plasma on day 3 post-ZIKV challenge. At approximately 45 days gestation (17-18 days post-challenge), two of the three dams were found with nonviable embryos by ultrasound. Viral RNA was detected in recovered tissues and at the maternal-fetal interface (MFI) in both cases. The remaining viable pregnancy proceeded to near term (~155 days gestational age) and ZIKV RNA was detected at the MFI but not in fetal tissues. These results suggest that sexual transmission of ZIKV may represent an underappreciated risk of pregnancy loss during early gestation.

Original languageEnglish (US)
Article number686437
JournalFrontiers in immunology
Volume12
DOIs
StatePublished - May 17 2021

Bibliographical note

Funding Information:
We thank the research, animal care, and veterinary staff at the California National Primate Research Center for caring for the animals and supporting this study amid the emerging SARS-CoV-2 pandemic. We also thank DHHS/PHS/NIH for providing the supplemental funding for R01 A1116382-01A1 that allowed this work to be completed. These studies were also supported by the California National Primate Research Center base operating grant #OD011107. In vivo imaging was performed with instrumentation funded by an NIH S10 grant #OD016261.

Publisher Copyright:
© Copyright © 2021 Newman, Tarantal, Martinez, Simmons, Morgan, Zeng, Rosinski, Bliss, Bohm, Dudley, Aliota, Friedrich, Miller and O’Connor.

Keywords

  • Zika virus
  • embryonic loss
  • intravaginal infection
  • macaques
  • pregnancy

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural

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