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2022-Das et al-Biology-Astrocyte Control of Zika Infection Is Independent of Interferon Type I and Type III Expression.pdf (9.01 MB)

Astrocyte Control of Zika Infection Is Independent of Interferon Type I and Type III Expression

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posted on 2022-05-13, 03:19 authored by Mithun DasMithun Das, Monique SmithMonique Smith, T Furihata, Subir SarkerSubir Sarker, R O’shea, Karla HelbigKarla Helbig
Zika virus (ZIKV) is a pathogenic neurotropic virus that infects the central nervous system (CNS) and results in various neurological complications. Astrocytes are the dominant CNS cell producer of the antiviral cytokine IFN-β, however little is known about the factors involved in their ability to mediate viral infection control. Recent studies have displayed differential responses in astrocytes to ZIKV infection, and this study sought to elucidate astrocyte cell-specific responses to ZIKV using a variety of cell models infected with either the African (MR766) or Asian (PRVABC59) ZIKV strains. Expression levels of pro-inflammatory (TNF-α and IL-1β) and inflammatory (IL-8) cytokines following viral infection were low and mostly comparable within the ZIKV-resistant and ZIKV-susceptible astrocyte models, with better control of proinflammatory cytokines displayed in resistant astrocyte cells, synchronising with the viral infection level at specific timepoints. Astrocyte cell lines displaying ZIKV-resistance also demonstrated early upregulation of multiple antiviral genes compared with susceptible astrocytes. Interestingly, pre-stimulation of ZIKV-susceptible astrocytes with either poly(I:C) or poly(dA:dT) showed efficient protection against ZIKV compared with pre-stimulation with either recombinant IFN-β or IFN-λ, perhaps indicating that a more diverse antiviral gene expression is necessary for astrocyte control of ZIKV, and this is driven in part through interferon-independent mechanisms.


This research was funded by La Trobe University's `understanding disease' Research Focus Area (RFA) grant. Additional support was provided by La Trobe University in the form of a La Trobe University Postgraduate Research Scholarship (LTUPRS) and La Trobe University Full Fee Research Scholarship (LTUFFRS).


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© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// 4.0/).