Early Embryonic Loss Following Intravaginal Zika Virus Challenge in Rhesus Macaques.

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

doi:10.3389/fimmu.2021.686437

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.

Highlights

Zika virus (ZIKV) emerged from relative obscurity five years ago to sweep through tropical and subtropical regions of the Western hemisphere
Dam 049-102 was positive for ZIKV RNA in blood plasma collected at hysterotomy, the last time point sampled for the study
ZIKV RNA was detected at the maternal-fetal interface (MFI) and in embryonic tissues, as well as in the amniotic fluid from the pregnancies of dams 049-102 and 049-103, supporting a role for ZIKV in the adverse pregnancy outcomes for these animals

Summary

Introduction

Zika virus (ZIKV) emerged from relative obscurity five years ago to sweep through tropical and subtropical regions of the Western hemisphere. Human infection with ZIKV can occur following mosquito-borne, vertical, and sexual transmission [5,6,7]. The majority of sexually-transmitted cases in non-endemic areas are likely the result of infection of the primary cases during travel, followed by inadvertent transmission to the secondary cases upon returning home [7]. Sexually-transmitted ZIKV infections in endemic areas or areas experiencing active outbreaks are difficult to differentiate from mosquitotransmitted infections because there may be an individual risk of exposure by either route. Studies have recently shown that intimate partners of household index cases are more likely to be positive or show serologic evidence of ZIKV infection relative to other members of the same household [21]

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