Congenital Zika Syndrome in Guinea Pigs

Abstract

Zika virus (ZIKV) infection during pregnancy may cause diverse and serious congenital defects in the developing fetus. In this study, we utilized pregnant guinea pigs to study congenital Zika syndrome. Female guinea pigs early in pregnancy (weeks 3–4 of gestation) were inoculated with Asian ZIKV strain (PRVABC59) or PBS (mock) via subcutaneous route. Dams were weighed daily, and blood and urine were collected at regular intervals to assess the presence of virus. Weight loss was observed in ZIKV-infected dams during first week of the infection. ZIKV-infected animals seroconverted with significant viremia and viral secretion in the urine. During the period between infection and delivery of the pups, significant viral RNA and NS1 protein were detected in all animals from 2 to 5 days after infection, with peak viral replication at day 3. We also detected robust viral RNA shedding in urine, with a prolonged duration relative to that of viremia. Dams developed remarkably robust ZIKV-specific neutralizing antibody response, and anti-ZIKV antibodies were also recovered from pups. Notably, ZIKV was efficiently transmitted from infected guinea pigs to their naïve co-caged mates. ZIKV infection of pregnant guinea pigs caused fetal damage. Sixty percent of ZIKV-infected dams showed abnormal pregnancies in that they all delivered at least one or more abnormal pup. Pups from ZIKV-infected animals exhibited significant intrauterine growth retardation. ZIKV was detected in the brain of pups from ZIKV-infected animals. ZIKV RNA and anti-ZIKV antibody levels in the dams reliably predicted abnormalities in pups. ZIKV detection in the brain tissues correlated with the pup abnormalities. In conclusion, the pregnant guinea pig model provides quantifiable congenital abnormality readouts to assess pregnancy outcomes; and may serve as a good model to test therapeutics, and to elucidate the mechanisms of ZIKV congenital pathogenesis.