Assessing Zika virus replication and the development of Zika-specific antibodies after a mid-gestation viral challenge in guinea pigs

PLoS One. 2017 Nov 3;12(11):e0187720. doi: 10.1371/journal.pone.0187720. eCollection 2017.

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.

MeSH terms

  • Animals
  • Antibodies, Viral / biosynthesis*
  • Disease Models, Animal*
  • Female
  • Guinea Pigs
  • Maternal-Fetal Exchange
  • Pregnancy
  • Pregnancy Complications, Infectious / immunology*
  • Viremia
  • Virus Replication*
  • Zika Virus / immunology
  • Zika Virus / pathogenicity
  • Zika Virus / physiology*
  • Zika Virus Infection / complications*
  • Zika Virus Infection / virology

Substances

  • Antibodies, Viral