MATERNAL ZIKA VIRUS (ZIKV) INFECTION FOLLOWING VAGINAL INOCULATION WITH ZIKV-INFECTED SEMEN IN THE TIMED-PREGNANT OLIVE BABOON.
Zika virus (ZIKV) infection is now firmly linked to congenital Zika Syndrome (CZS), including fetal microcephaly. While of mosquito are the primary vector for ZIKV, sexual transmission of ZIKV is a significant route of infection. ZIKV has been documented in human, mouse and non-human primate (NHP) semen. It is critical to establish NHP models of vertical transfer of ZIKV that recapitulate human pathogenesis. We hypothesized that vaginal deposition of ZIKV-infected baboon semen would lead to maternal infection and vertical transfer in the olive baboon (). Epidemiological studies suggest an increased rate of CZS in the Americas compared to the original link to CZS in French Polynesia, therefore we also compared the French Polynesian ZIKV isolate (FP) to the Puerto Rican isolate (PR). Timed pregnant baboons (n=6) were inoculated via vaginal deposition of baboon semen containing 10 ffu ZIKV (n=3, FP isolate:H/PF/2013, n=3 PR isolate:PRVABC59) at mid-gestation (86-95 days gestation [lsqb]dG[rsqb]; term 183dG) on day (d) 0 (all dams), and then at 7 day intervals through three weeks. Maternal blood, saliva and cervico-vaginal washes (cvw) were obtained. Animals were euthanized at 28 (n=5) or 39 (n=1) days post initial inoculation (dpi) and maternal/fetal tissues collected. Viremia was achieved in 3/3 FP ZIKV infected dams and 2/3 PR ZIKV. ZIKV RNA was detected in cvw in 5/6 dams. ZIKV RNA was detected in lymph nodes, but not ovary, uterus, cervix or vagina in FP isolate infected dams. ZIKV RNA was detected in lymph nodes (3/3), uterus (2/3) and vagina (2/3) in PR isolate infected dams. Placenta, amniotic fluid and fetal tissues were ZIKV RNA negative in the FP infected dams whereas 2/3 PR infected dam placentas were ZIKV RNA positive. We conclude that ZIKV infected semen is a means of ZIKV transmission during pregnancy in primates. The PR isolate appeared more capable of wide spread dissemination to tissues, including reproductive tissues and placenta compared to the FP isolate.Zika virus remains a worldwide health threat with outbreaks still occurring in the Americas. While mosquitos are the primary vector for spread of the virus, sexual transmission of Zika virus is also a significant means of infection, especially in terms of passage from an infected to uninfected partner. While sexual transmission has been documented in humans, and male to female transmission has been reported in mice, ours is the first in non-human primates to demonstrate infection via vaginal deposition of Zika infected semen. The latter is important since a recent publication indicated that human semen inhibited, in a laboratory setting, Zika infection of reproductive tissues. We also found that compared to the French Polynesian isolate that the Puerto Rican Zika isolate lead to greater spread through the body, in particular in reproductive tissues. The American isolates of Zika appear to have acquired mutations increasing their efficacy.Copyright © 2020 Gurung et al.