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Review
. 2019 Sep 29;6(1):481-500.
doi: 10.1146/annurev-virology-092818-015732. Epub 2019 Jun 10.

Using Macaques to Address Critical Questions in Zika Virus Research

Dawn M Dudley  1 , Matthew T Aliota  2 , Emma L Mohr  3 , Christina M Newman  1 , Thaddeus G Golos  4   5 , Thomas C Friedrich  4   6 , David H O'Connor  1   4
Affiliations
Review

Using Macaques to Address Critical Questions in Zika Virus Research

Dawn M Dudley et al. Annu Rev Virol. .

Abstract

Zika virus (ZIKV) and nonhuman primates have been inextricably linked since the virus was first discovered in a sentinel rhesus macaque in Uganda in 1947. Soon after ZIKV was epidemiologically associated with birth defects in Brazil late in 2015, researchers capitalized on the fact that rhesus macaques are commonly used to model viral immunity and pathogenesis, quickly establishing macaque models for ZIKV infection. Within months, the susceptibility of pregnant macaques to experimental ZIKV challenge and ZIKV-associated abnormalities in fetuses was confirmed. This review discusses key unanswered questions in ZIKV immunity and in the pathogenesis of thecongenital Zika virus syndrome. We focus on those questions that can be best addressed in pregnant nonhuman primates and lessons learned from developing macaque models for ZIKV amid an active epidemic.

Keywords: ZIKV; Zika virus; arbovirus; congenital Zika syndrome; flavivirus; macaque; pregnant.

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Figures

Figure 1.
Figure 1.
Depiction of stages of prenatal development that have been shown to be impacted by maternal infection with ZIKV, comparing the timeline of rhesus macaque and human fetal development. Developmental milestones include embryo implantation and placenta formation (e.g., placental insufficiency), development of the eye (e.g., choroidal coloboma), cerebellum (e.g., vermis agenesis), cerebral cortex (cortical simplification), and development of the immune system. The macaque and human immune systems are well-developed at birth and are able to mount immune responses to pathogens.
Figure 2.
Figure 2.
Stages of postnatal development that have been shown to be impacted by maternal infection with ZIKV, or may be identified as affected by congenital ZIKV exposure in long term clinical studies. Postnatal milestones include birth (e.g., higher miscarriage and stillbirth rates in ZIKV-exposed pregnancies), neurological milestones such as caregiver interactions, vision, and gross motor function (e.g. abnormal neurological or neuromuscular development in CZS), and life stage milestones including puberty and aging (these life stages have not been studied in ZIKV congenitally-exposed humans yet). Some children with severe CZS have decreased life expectancy compared with their unaffected human counterparts and it is remains unclear whether less affected infants with CZS will have altered life expectancies compared with their unaffected human counterparts.
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References

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