Flavivirus replication kinetics in early-term placental cell lines with different differentiation pathways

Julio Carrera,Jason M Mackenzie,Alice M Trenerry,Cameron P Simmons

doi:10.1186/s12985-021-01720-y

Julio Carrera, Jason M Mackenzie + Show 2 more

Open Access

https://doi.org/10.1186/s12985-021-01720-y

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Abstract

BackgroundThe uncontrollable spread of Zika virus (ZIKV) in the Americas during 2015–2017, and its causal link to microcephaly in newborns and Guillain-Barré syndrome in adults, led the World Health Organisation to declare it a global public health emergency. One of the most notable features of ZIKV pathogenesis was the ability of the virus to pass the placental barrier to infect the growing foetus. This pathogenic trait had not been observed previously for medically important flaviviruses, including dengue and yellow fever viruses.MethodsIn this study we evaluated the replication kinetics of ZIKV and the related encephalitic flavivirus West Nile strain Kunjin virus (WNVKUN) in early-term placental cell lines.ResultsWe have observed that WNVKUN in fact replicates with a greater rate and to higher titres that ZIKV in these cell lines.ConclusionsThese results would indicate the potential for all flaviviruses to replicate in placental tissue but it is the ability to cross the placenta itself that is the restrictive factor in the clinical progression and presentation of congenital Zika syndrome.

Highlights

The uncontrollable spread of Zika virus (ZIKV) in the Americas during 2015–2017, and its causal link to microcephaly in newborns and Guillain-Barré syndrome in adults, led the World Health Organisation to declare it a global public health emergency
HTR8/SVneo and BeWo cells are both trophoblastic cell lines originated from a first trimester placenta; BeWo cells are a representative of the villous pathway that remains within the placenta and HTR8/SVneo cells are a representative of the extravillious pathway, which migrate and infiltrate into the maternal decidua where they play important functions by interacting with cells in the stroma and modify blood vessels [10]
Slides were stored at 4 °C and cells were analyzed using a Zeiss 710 Confocal Microscope and ZenTM Zeiss ® software. Both West Nile and Zika virus infection of cells of placental origin release high titres of infectious virus To evaluate the replication of W NVKUN and ZIKV in the different placental cell lines we initially assessed the infect rates by FACS analysis (Fig. 1A–C)

Summary

Introduction

The uncontrollable spread of Zika virus (ZIKV) in the Americas during 2015–2017, and its causal link to microcephaly in newborns and Guillain-Barré syndrome in adults, led the World Health Organisation to declare it a global public health emergency. As infection progressed it was shown that ZIKV had a distinctive tropism for the central nervous system (CNS) of the developing embryo, which led to microcephaly, an extreme manifestation of the recognized congenital Zika syndrome. This new teratogenic syndrome includes a full range of other neurological complications such as spasticity, seizures, brainstem disfunction, The transfer of ZIKV to the foetus through the placenta occurs after the colonization of the decidua, whose cells are permissive to the infection of several viruses including ZIKV. It becomes imperative to understand other flaviviruses such as DENV or West Nile virus (WNV) from this point of view, since mutations in these viruses could potentially confer ZIKV characteristics to other flaviviruses

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