Neuron · 2022
Myeloid cell interferon secretion restricts Zika flavivirus infection of developing and malignant human neural progenitor cells.
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Bulstrode Harry, Girdler Gemma C, Gracia Tannia, Aivazidis Alexander, Moutsopoulos Ilias, Young Adam M H, Hancock John, He Xiaoling, Ridley Katherine, Xu Zhaoyang, Stockley John H, Finlay John, Hallou Clement, Fajardo Teodoro, Fountain Daniel M, van Dongen Stijn, Joannides Alexis, Morris Robert, Mair Richard, Watts Colin, Santarius Thomas, Price Stephen J, Hutchinson Peter J A, Hodson Emma J, Pollard Steven M, Mohorianu Irina, Barker Roger A, Sweeney Trevor R, Bayraktar Omer, Gergely Fanni, Rowitch David H
Аннотация
Zika virus (ZIKV) can infect human developing brain (HDB) progenitors resulting in epidemic microcephaly, whereas analogous cellular tropism offers treatment potential for the adult brain cancer, glioblastoma (GBM). We compared productive ZIKV infection in HDB and GBM primary tissue explants that both contain SOX2+ neural progenitors. Strikingly, although the HDB proved uniformly vulnerable to ZIKV infection, GBM was more refractory, and this correlated with an innate immune expression signature. Indeed, GBM-derived CD11b+ microglia/macrophages were necessary and sufficient to protect progenitors against ZIKV infection in a non-cell autonomous manner. Using SOX2+ GBM cell lines, we found that CD11b+-conditioned medium containing type 1 interferon beta (IFNβ) promoted progenitor resistance to ZIKV, whereas inhibition of JAK1/2 signaling restored productive infection. Additionally, CD11b+ conditioned medium, and IFNβ treatment rendered HDB progenitor lines and explants refractory to ZIKV. These findings provide insight into neuroprotection for HDB progenitors as well as enhanced GBM oncolytic therapies.