Infectivity of Zika virus on primary cells support tree shrew as animal model

Emerg Microbes Infect. 2019;8(1):232-241. doi: 10.1080/22221751.2018.1559707.

Abstract

Zika virus (ZIKV) is a mosquito-borne flavivirus that caused the public health emergency. Recently, we have proved a novel small animal tree shrew was susceptive to ZIKV infection and presented the most common rash symptoms as ZIKV patients. Here we further cultured the primary cells from different tissues of this animal to determine the tissue tropism of ZIKV infection in vitro. The results showed that the primary cells from tree shrew kidney, lung, liver, skin and aorta were permissive to ZIKV infection and could support viral replication by the detection of viral specific RNA intra- and extra-cells. In comparing, the skin fibroblast and vascular endothelial cells were highly permissive to ZIKV infection with high releasing of active virus particles in supernatants proved by its infectivity in established neonatal mouse model. The expressions of ZIKV envelop and nonstructural protein-1, and the effects and strong immune response of primary tree shrew cells were also detected followed by ZIKV infection. These findings provide powerful in vitro cell-level evidence to support tree shrew as animal model of ZIKV infection and may help to explain the rash manifestations in vivo.

Keywords: Zika virus; infectivity; primary cells; tree shrew; tropism.

MeSH terms

  • Animals
  • Aorta / cytology
  • Aorta / virology
  • Cells, Cultured
  • Chlorocebus aethiops
  • Disease Models, Animal*
  • HEK293 Cells
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Kidney / cytology
  • Kidney / virology
  • Liver / cytology
  • Liver / virology
  • Lung / cytology
  • Lung / virology
  • Skin / cytology
  • Skin / virology
  • Tupaiidae / virology*
  • Vero Cells
  • Virus Replication
  • Zika Virus / pathogenicity*
  • Zika Virus Infection / virology*

Grants and funding

This work was supported by the National Natural Science Foundation of China (NSFC) under grant No.U1702282 and No. 81471937; the Yunnan provincial Innovative Team Project under grant No.2015HC030; the Excellent Young Scientist Program under grant No. 81522025; the Innovative Research Group of the NSFC under grant No. 81621005 and the Newton Advanced Fellowship from the UK Academy of Medical Sciences under grant No. NAF003\1003.