Abstract

Primary Zika virus (ZIKV) infections that occur during pregnancy can cause spontaneous abortion and profoundly disrupt fetal development. While the full range of developmental abnormalities associated with congenital Zika syndrome is not yet known, severe cases of the syndrome can present with microcephaly, extensive neurologic and ocular damage, and pronounced joint malformations. Animal models that accurately recapitulate congenital Zika syndrome are urgently needed for vaccine development and for the study of ZIKV pathogenesis. As guinea pigs have successfully been used to model transplacental infections by cytomegalovirus, syphilis, and Listeria monocytogenes, we sought to test whether ZIKV could productively infect guinea pigs and whether viral transmission with attendant fetal pathology would occur after a mid-gestation viral challenge. We found that guinea pig cells supported ZIKV replication in vitro. Experimental infection of non-pregnant animals did not result in overt disease but low-level, detectable viremia was observed. When pregnant guinea pigs were challenged with ZIKV at between 18 and 21 days gestational age, ZIKV was not detected in maternal or pup blood, plasma, or tissues and no significant differences in maternal weight gain or pup size were observed following challenge. Nonetheless, a robust antibody response against ZIKV was detected in both the pups and dams. These results suggest that, while guinea pigs can model aspects of the immune response to ZIKV infection during pregnancy, naturally circulating ZIKV strains are not pathogenic during the pregnancy of immunocompetent guinea pigs and do not interfere with normal pup development.

Highlights

  • Zika virus (ZIKV) is an emerging, mosquito-borne flavivirus that can be transmitted transplacentally and disrupt the normal development of human fetuses

  • A robust antibody response against ZIKV did develop in the infected dams and anti-ZIKV antibodies were recovered from their pups. These results suggest that naturally occurring ZIKV strains are immunologically well-controlled by pregnant guinea pigs and that either immune suppression or host-adaptation of ZIKV strains will be necessary if a guinea pig model of congenital Zika syndrome is to be developed

  • To determine whether ZIKV can replicate in guinea pig cells in vitro, guinea pig lung fibroblasts (JH4) and Vero cells were infected at a low multiplicity of infection (MOI)

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Summary

Introduction

Zika virus (ZIKV) is an emerging, mosquito-borne flavivirus that can be transmitted transplacentally and disrupt the normal development of human fetuses. Prior to the recent outbreaks in the Pacific and Americas, ZIKV infection was believed to only cause a mild febrile illness characterized by fever, rash, arthralgia, myalgia, headache, and conjunctivitis [1]. ZIKV associated Guillain-Barresyndrome was initially observed during the 2013 outbreak in French. Zika virus challenge during guinea pig pregnancy role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

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