Recapitulating Zika Virus Infection in Vagina of Tree Shrew (Tupaia belangeri).

Zulqarnain Baloch,Jiejie Dai,Li Zhang,Yue Feng,Zifeng Yang,Na-Na Zhang,Cheng-Feng Qin,Zhili Shen,Xiaomei Sun,Chunguang Yang,Yong-Qiang Deng,Xueshan Xia,Daoqun Li

doi:10.3389/fcimb.2021.687338

Abstract

Sexual transmission of Zika Virus (ZIKV) elevates the risk of its dissemination in the female reproductive tract and causes a serious threat to the fetus. However, the available animal models are not appropriate to investigate sexual transmission, dynamics of ZIKV infection, replication, and shedding. The use of tree shrew as a small animal model of ZIKV vaginal infection was assessed in this study. A total of 23 sexually mature female tree shrews were infected with ZIKV GZ01 via the intravaginal route. There was no significant difference in change of body weight, and the temperature between ZIKV infected and control animals. Viral RNA loads were detected in blood, saliva, urine, and vaginal douching. ZIKV RNA was readily detected in vaginal lavage of 22 animals (95.65%, 22/23) at 1 dpi, and viral load ranged from 104.46 to 107.35 copies/ml, and the peak of viral load appeared at 1 dpi. The expression of key inflammatory genes, such as IL6, 8, CCL5, TNF-a, and CXCL9, was increased in the spleen of ZIKV infected animals. In the current study, female tree shrews have been successfully infected with ZIKV through the vaginal route for the first time. Interestingly, at first, ZIKV replicates at the local site of infection and then spreads throughout the host body to develop a robust systemic infection and mounted a protective immune response. This small animal model is not only valuable for exploring ZIKV sexual transmission and may also help to explain the cause of debilitating manifestations of the fetus in vivo.

Highlights

Zika virus, a member of the Flaviviridae family first reported in 1947 (Wikan and Smith, 2016), is an arthropod-based-vector-born virus (Epelboin et al, 2017)
To further characterize Zika Virus (ZIKV) vaginal infection dynamics in tree shrews, blood, saliva, urine, and vaginal douching samples were collected from animals and subjected to virological assays
ZIKV viremia was detected in 17.39% (4/23) tree shrews at 5 dpi and 21.74% (5/ 23) at 7dpi, and the viral loads in serum ranged from 104.85 to 105.6 copies/ml (Figure 2B) and became undetectable at 10 dpi

Summary

Introduction

A member of the Flaviviridae family first reported in 1947 (Wikan and Smith, 2016), is an arthropod-based-vector-born virus (Epelboin et al, 2017). Rodent model is not always an appropriate model for ZIKV Another leading unanticipated consequence of ZIKV infection is sexual transmission. The application of rodent models to study the vertical or sexual transmission of ZIKV infection is further limited. NHPs are valuable models for investigation of the basic and applied research of human viral infections including ZIKV (Osuna et al, 2016; Mohr, 2018) but the application of NHPs in biomedical research is very limited (only one-half of the one percent) due to serious ethical and practical concerns (Friedman et al, 2017). There is a critical need for alternative animal models of ZIKV that certainly develop infections like humans and can be a more appropriate animal model

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