Study of teratogenic and abortogenic potential of ZIKV infection at different gestational times in sheep 

Sheep represent a unique model for human pregnancy due to longer gestation and a comparable fetal development rate; furthermore, this species is highly susceptible to many teratogenic viruses acting like Zika. ZIKA-PATHO established the feasibility of sheep as a model for Zika infection evaluating Zika vertical transmission in early and mid ovine gestation. This model was further assessed characterizing Zika replication in adult and fetal ovine cell lines by in vitro experiments.  Finally, ZIKA-PATHO investigated Zika sexual transmission using male sheep as a model for male human reproductive tract.  

Who was involved

This was led by University of Florida.  

Results

Zika infection of pregnant sheep resulted in a change in fetal growth and gestational outcomes. When the infection was conducted during the early gestational period, it caused fetal loss, reduction of fetal cranial circumference and a decrease of fetal brain weight. Despite numerous clinical signs, viral RNA was detected only in peripheral blood mononuclear cells in the first-week post-infection. Differently, when pregnant ewe were infected during the mid gestational period, a wider and more severe viral replication was observed. In fact, Zika RNA was detected in maternal placenta and spleen, and in fetal organs including the brains, spleens, liver, and umbilicus of infected fetuses. Moreover, fetuses of infected sheep had visibly misshapen heads with significantly smaller head sizes when compared to controls. Finally, a strong Zika replication was found also in infected ram and involved spleen, liver, testes/epididymides and accessory sex glands. In both experiments, starting from the four-week post infection, Zika neutralizing antibodies were detected in all infected animals. Interestingly, those antibodies were tested for their neutralization capacity against three different Zika strains, two belonging to the Asian lineage and one to the African lineage. The results showed that all Zika virus strains were 50% neutralized by infected ewe sera confirming a similar antigenic behaviour among the lineages tested.