Zika Virus Induced More Severe Inflammatory Response Than Dengue Virus in Chicken Embryonic Livers

Zongyi Zhang,Jieping Deng,Wei Zhao,Guobing Chen,Menghan Sun,Xuesong Yang,Jianhai Yu,Pengcheng Wang

doi:10.3389/fmicb.2019.01127

Zongyi Zhang, Jieping Deng + Show 6 more

Open Access

https://doi.org/10.3389/fmicb.2019.01127

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Abstract

Dengue (DENV) and Zika virus (ZIKV) are important flaviviruses in tropical and subtropical regions, causing severe Dengue Hemorrhagic Fever (DHF)/Dengue Shock Syndrome (DSS) and microcephaly, respectively. The infection of both viruses during pregnancy were reported with adverse fetal outcomes. To investigate the effects of ZIKV and DENV infections on fetal development, we established an infection model in chicken embryos. Compared with DENV-2, the infection of ZIKV significantly retarded the development of chicken embryos. High viral loads of both DENV-2 and ZIKV was detected in brain, eye and heart 7 and 11 days post-infection, respectively. Interestingly, only ZIKV but not DENV-2 was detected in the liver. Even both of them induced apparent liver inflammation, ZIKV infection showed a more severe inflammatory response than DENV-2 infection based on the inflammation scores and the gene expression levels of IL-1β, TNF, IL-6, and TGFβ-2 in liver. Our results demonstrated that ZIKV induced more severe inflammatory response in chicken embryo liver compared to DENV-2, which might partially attribute to viral replication in liver cells. Clinicians should be aware of the potential liver injury associated with ZIKV infection in patients, especially in perinatal fetuses.

Highlights

Dengue virus (DENV) is one of the most important arboviruses in tropical and subtropical regions, and it belongs to the family Flaviviridae, including four distinct serotypes designated DENV-1, DENV-2, DENV-3, and DENV-4, which cause mild Dengue Fever and more severe Dengue Hemorrhagic Fever (DHF) and Dengue Shock Syndrome (DSS) (Halstead, 1989)
Chicken embryos were infected with DENV-2 NGC strain or a Zika virus (ZIKV) isolated from a human subject traveled to the epidemic area
ZIKV belongs to flavivirus genus and draws great attention since 2015 because of its infection in pregnant women potentially leading to severe neurological mal-development, microcephaly, in fetuses

Summary

Introduction

Dengue virus (DENV) is one of the most important arboviruses in tropical and subtropical regions, and it belongs to the family Flaviviridae, including four distinct serotypes designated DENV-1, DENV-2, DENV-3, and DENV-4, which cause mild Dengue Fever and more severe Dengue Hemorrhagic Fever (DHF) and Dengue Shock Syndrome (DSS) (Halstead, 1989). Besides the febrile disease in general population caused by DENV, there have been concerns about the effects on fetuses due to the viral infection in pregnant women. The infection in pregnant women could cause severe neurological damages, like microcephaly, in fetuses (Driggers et al, 2016; Mlakar et al, 2016). It’s reported that ZIKV could infect placental trophoblasts (Tabata et al, 2016; Aagaard et al, 2017; Sheridan et al, 2017) and virus genome was found in the tissues of infected mothers and neonates with microcephaly (Calvet et al, 2016; Melo et al, 2016), which indicated that ZIKV could be vertically transmitted, probably in a transplacental manner, but the mechanisms of how exactly the virus is passed to the fetuses are still obscure

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