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Zika virus co-opts miRNA networks to persist in placental microenvironments detected by spatial transcriptomics [AGO-HITS-CLIP]

ABSTRACT: We and others have demonstrated Zika virus (ZIKV) congenital infection evades double-stranded RNA detection, and may persist in the placenta for the duration of pregnancy without accompanying overt histopathologic inflammation. We used orthogonal approaches to test the hypothesis that ZIKV disrupts placental miRNAs to enable viral persistence and fetal pathogenesis. In primary human trophoblasts, high-throughput sequencing crosslinking and immunoprecipitation (AGO-HITS-CLIP) demonstrated an unexpected disruption of placental miRNA-regulated TGF-β networks. In gnotobiotic mice, absence of microbes rendered normally resistant mice susceptible to congenital ZIKV infection, and placental spatial transcriptomics revealed distinct microenvironments defined by significant upregulation of complement cascade components. Finally, treatment of ZIKV-infected mice with the RNAi-enhancer enoxacin led to loss of ZIKV placental persistence and rescue of fetal growth restriction. These results collectively suggest that ZIKV co-opts miRNA inflammatory regulatory networks to persist in the placenta reservoir, a conduit of vertical transmission and fetal pathogenesis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE205609 | GEO | 2023/06/03

REPOSITORIES: GEO

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Zika virus co-opts miRNA networks to persist in placental microenvironments detected by spatial transcriptomics [visium]

Project description:We and others have demonstrated Zika virus (ZIKV) congenital infection evades double-stranded RNA detection, and may persist in the placenta for the duration of pregnancy without accompanying overt histopathologic inflammation. We used orthogonal approaches to test the hypothesis that ZIKV disrupts placental miRNAs to enable viral persistence and fetal pathogenesis. In primary human trophoblasts, high-throughput sequencing crosslinking and immunoprecipitation (AGO-HITS-CLIP) demonstrated an unexpected disruption of placental miRNA-regulated TGF-β networks. In gnotobiotic mice, absence of microbes rendered normally resistant mice susceptible to congenital ZIKV infection, and placental spatial transcriptomics revealed distinct microenvironments defined by significant upregulation of complement cascade components. Finally, treatment of ZIKV-infected mice with the RNAi-enhancer enoxacin led to loss of ZIKV placental persistence and rescue of fetal growth restriction. These results collectively suggest that ZIKV co-opts miRNA inflammatory regulatory networks to persist in the placenta reservoir, a conduit of vertical transmission and fetal pathogenesis.

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Zika virus co-opts miRNA networks to persist in placental microenvironments detected by spatial transcriptomics

Project description:Zika virus co-opts miRNA networks to persist in placental microenvironments detected by spatial transcriptomics

| PRJNA846741 | ENA

Zika virus co-opts miRNA networks to persist in placental microenvironments detected by spatial transcriptomics [visium]

Project description:Zika virus co-opts miRNA networks to persist in placental microenvironments detected by spatial transcriptomics [visium]

| PRJNA846745 | ENA

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