Translational Model of Zika Virus Disease in Baboons

J Virol. 2018 Jul 31;92(16):e00186-18. doi: 10.1128/JVI.00186-18. Print 2018 Aug 15.

Abstract

Zika virus (ZIKV) is an emerging mosquito-borne flavivirus with devastating outcomes seen recently in the Americas due to the association of maternal ZIKV infection with fetal microcephaly and other fetal malformations not previously associated with flavivirus infections. Here, we have developed the olive baboon (Papio anubis) as a nonhuman primate (NHP) translational model for the study of ZIKV pathogenesis and associated disease outcomes to contrast and compare with humans and other major NHPs, such as macaques. Following subcutaneous inoculation of adult male and nonpregnant female baboons, viremia was detected at 3 and 4 days postinfection (dpi) with the concordant presentation of a visible rash and conjunctivitis, similar to human ZIKV infection. Furthermore, virus was detected in the mucosa and cerebrospinal fluid. A robust ZIKV-specific IgM and IgG antibody response was also observed in all the animals. These data show striking similarity between humans and the olive baboon following infection with ZIKV, suggesting our model is a suitable translational NHP model to study ZIKV pathogenesis and potential therapeutics.IMPORTANCE ZIKV was first identified in 1947 in a sentinel rhesus monkey in Uganda and subsequently spread to Southeast Asia. Until 2007, only a small number of cases were reported, and ZIKV infection was relatively minor until the South Pacific and Brazilian outbreaks, where more severe outcomes were reported. Here, we present the baboon as a nonhuman primate model for contrast and comparison with other published animal models of ZIKV, such as the mouse and macaque species. Baboons breed year round and are not currently a primary nonhuman primate species used in biomedical research, making them more readily available for studies other than human immunodeficiency virus studies, which many macaque species are designated for. This, taken together with the similarities baboons have with humans, such as immunology, reproduction, genetics, and size, makes the baboon an attractive NHP model for ZIKV studies in comparison to other nonhuman primates.

Keywords: West Nile virus; ZIKV; Zika virus; baboon; flavivirus; nonhuman primate.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Viral / metabolism*
  • Brazil
  • Disease Models, Animal*
  • Female
  • Humans
  • Immunoglobulin G / metabolism
  • Immunoglobulin M / metabolism
  • Male
  • Mucous Membrane / virology
  • Papio
  • Viremia / cerebrospinal fluid
  • Viremia / diagnosis*
  • Zika Virus / immunology
  • Zika Virus / pathogenicity*
  • Zika Virus Infection / cerebrospinal fluid
  • Zika Virus Infection / diagnosis*
  • Zika Virus Infection / immunology

Substances

  • Antibodies, Viral
  • Immunoglobulin G
  • Immunoglobulin M