Nonhuman Primate Models of Zika Virus Infection and Disease during Pregnancy

Abstract

Since the explosive outbreak of Zika virus in Brazil and South/Central America in 2015-2016, the frequency of infections has subsided, but Zika virus remains present in this region as well as other tropical and sub-tropical areas of the globe. The most alarming aspect of Zika virus infection is its association with severe birth defects when infection occurs in pregnant women. Understanding the mechanism of Zika virus pathogenesis, which comprises features unique to Zika virus as well as shared with other teratogenic pathogens, is key to future prophylactic or therapeutic interventions. Nonhuman primate-based research has played a significant role in advancing our knowledge of Zika virus pathogenesis, especially with regard to fetal infection. This review summarizes what we have learned from these models and potential future research directions.

Keywords: immune response; nonhuman primate; placenta; pregnancy; zika virus.

Figure 1

Zika related uteroplacental pathology. (A) Gestational age-matched negative control placental histology. In contrast, Zika infected placentas (B,C) are more likely to have lobular infarctions (*) and villous stromal microcalcifications (arrows). Early stages of villous stromal cell death are also seen (inset arrowhead). (D) Some cases have maternal decidual leukocytoclastic vasculitis composed of lymphocytes, plasma cells, and eosinophils (arrow). (E) Preliminary data in NHP models suggest a potential relationship with chronic histiocytic intervillositis (*), which is supported by CD68-positive macrophages (*) in the intervillous space around viable villi (F). Photomicrographs of hemotoxylin- and eosin-stained sections (A–E), as well as immunohistochemical stained section with hematoxylin counterstain. Bar is 100 µm.