Modeling Congenital Zika Syndrome in Guinea Pigs

Objectives: Zika virus (ZIKV) infection during pregnancy is teratogenic, disrupting fetal neurodevelopment and causing severe birth defects including microcephaly. Animal models that recapitulate congenital Zika syndrome are needed for vaccine development and for the study of ZIKV pathogenesis. Guinea pigs and humans have morphologically similar placentas and the ~65 day guinea pig gestation can be divided into trimesters that are developmentally analogous to those of humans. As guinea pigs have successfully been used to model transplacental infections by cytomegalovirus, syphilis, and Listeria monocytogenes, we sought to test whether ZIKV could cause infections with attendant fetal pathology during pregnancy.

Methods: Adult Hartley guinea pigs were challenged with ZIKV H/PF/2013, a strain recovered from the 2013 French Polynesian outbreak. Non-pregnant animals were weighed daily, bled every other day, and euthanized at fourteen days post infection. Timed mated dams were infected at 22-24 days gestational age. Pregnant guinea pigs were weighed daily, bled weekly, and euthanized with their pups on the day of delivery. The ZIKV viral load in blood and tissue was quantified by qRT-PCR and the immune response to ZIKV was measured by direct ELISA against NS1.

Results: We found that guinea pig cells supported ZIKV replication in vitro. Experimental infection of non-pregnant animals did not result in overt disease, but transient viremia was detected. Pregnant guinea pigs infected early during the second trimester had reduced weight gain compared to uninfected dams or guinea pigs infected with cytomegalovirus. Pups born to ZIKV infected animals were significantly smaller than historic controls, and a robust antibody response against ZIKV NS1 was detected in both the pups and dams.

Conclusions: These results indicate that guinea pigs are permissive to ZIKV infection. While non-pregnant animals are sub-clinically infected, infection during guinea pig pregnancy results in intrauterine growth restriction, suggesting that guinea pigs may be a model of congenital ZIKV syndrome.