Zika virus alters DNA methylation status of genes involved in Hippo signaling pathway in human neural progenitor cells

Kandilya, Deepika; Maskomani, Silambarasan; Sudhaharan, Sukanya; Tambyah, Paul Anantharajah; Chan, Shiao-Yng; Lee, Regina Ching Hua; Hande, M. Prakash; Mallilankaraman, Karthik; Chu, Justin Jang Hann; Dheen, S. Thameem

doi:10.2217/epi-2018-0180

Cited by 18 publications

(17 citation statements)

References 49 publications

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“…The HIPPO pathway was also reported to be involved in the modulation of antiviral response by other virus infections, e.g., Sendai virus [39]. Recently, it was reported to be implicated in Zika-virus induced microcephaly [40]. These reported results suggested that the involvement of the HIPPO signaling pathway during virus infection can either lead to an overactive induction resulting in cancer, or cross-talk with other signaling cascade to maintain the virus in an antiviral state.…”

Section: Discussionmentioning

confidence: 94%

A System Based-Approach to Examine Host Response during Infection with Influenza A Virus Subtype H7N9 in Human and Avian Cells

Taye

Chen

Yeo

et al. 2020

Cells

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Although the influenza A virus H7N9 subtype circulates within several avian species, it can also infect humans with a severe disease outcome. To better understand the biology of the H7N9 virus we examined the host response to infection in avian and human cells. In this study we used the A/Anhui/1/2013 strain, which was isolated during the first wave of the H7N9 epidemic. The H7N9 virus-infected both human (Airway Epithelial cells) and avian (Chick Embryo Fibroblast) cells, and each infected host transcriptome was examined with bioinformatic tools and compared with other representative avian and human influenza A virus subtypes. The H7N9 virus induced higher expression changes (differentially regulated genes) in both cell lines, with more prominent changes observed in avian cells. Ortholog mapping of differentially expression genes identified significant enriched common and cell-type pathways during H7N9 infections. This data confirmed our previous findings that different influenza A virus subtypes have virus-specific replication characteristics and anti-virus signaling in human and avian cells. In addition, we reported for the first time, the new HIPPO signaling pathway in avian cells, which we hypothesized to play a vital role to maintain the antiviral state of H7N9 virus-infected avian cells. This could explain the absence of disease symptoms in avian species that tested positive for the presence of H7N9 virus.

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Section: Discussionmentioning

confidence: 94%

A System Based-Approach to Examine Host Response during Infection with Influenza A Virus Subtype H7N9 in Human and Avian Cells

Taye

Chen

Yeo

et al. 2020

Cells

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“…Among these pathways, hippo and hedgehog signaling pathways have been shown to play crucial roles in cortical development [ 32 , 33 ]. Hence, we investigated m 6 A-methylation status in major genes among E-SMRs in these two pathways.…”

Section: Resultsmentioning

confidence: 99%

Unique and Specific m6A RNA Methylation in Mouse Embryonic and Postnatal Cerebral Cortices

Zhang

Wang

et al. 2020

Genes

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N6-methyladenosine (m6A)-mediated epitranscriptomic regulation is critical for various physiological processes. Genetic studies demonstrate that proper m6A-methylation is required for mouse brain development and function. Revealing landscapes of m6A-methylation in the cerebral cortex at different developmental stages will help to understand the biological meaning of epitranscriptomic regulation. Here, we depict the temporal-specific m6A-methylation status in mouse embryonic and postnatal cortices using methylated RNA immunoprecipitation (MeRIP) sequencing. We identified unique m6A binding motifs in stage-specific RNAs and found that more RNA transcripts are temporally methylated in embryonic cortices than in postnatal ones. Moreover, we found that cortical transcription factors and genes associated with neurological disorders are broadly as well specifically methylated at m6A sites. Our study highlights the importance of epitranscriptomic regulation in the developing cortex and provides a fundamental reference for future mechanistic examinations of m6A methylation-mediated gene expression regulation in normal brain development and neurological disorders.

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“…DNA methylation profiling reveals that ZIKV infection induces hypermethylation on genes of key signaling molecules in the Hippo signaling pathway, such as TAZ and RASSF1, resulting in a decrease in the protein expression. In addition, the expression level and phosphorylation of YAP/TAZ are significantly decreased in human neural progenitor cells (hNPCs) after ZIKV infection (Kandilya et al, 2019). These data suggest that ZIKV may inhibit cell proliferation by downregulating the Hippo signaling.…”

Section: Zika Virusmentioning

confidence: 91%

“…Zika virus (ZIKV) ZIKV infection induces hypermethylation of TAZ and RASSF1; YAP/TAZ and phosphorylated YAP/TAZ levels are significantly reduced in hNPCs after ZIKV infection. Kandilya et al, 2019 transcription factor c-Myb in HCC cells. Silencing of YAP abolishes the proliferation of hepatoma cells mediated by HBXIP in vitro and in vivo.…”

Section: He Et Al 2017mentioning

confidence: 99%

The Hippo Pathway and Viral Infections

Wang

Zhang

et al. 2020

Front. Microbiol.

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The Hippo signaling pathway is a novel tumor suppressor pathway, initially found in Drosophila. Recent studies have discovered that the Hippo signaling pathway plays a critical role in a wide range of biological processes, including organ size control, cell proliferation, cancer development, and virus-induced diseases. In this review, we summarize the current understanding of the biological feature and pathological role of the Hippo pathway, focusing particularly on current findings in the function of the Hippo pathway in virus infection and pathogenesis.

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Zika virus alters DNA methylation status of genes involved in Hippo signaling pathway in human neural progenitor cells

Cited by 18 publications

References 49 publications

A System Based-Approach to Examine Host Response during Infection with Influenza A Virus Subtype H7N9 in Human and Avian Cells

A System Based-Approach to Examine Host Response during Infection with Influenza A Virus Subtype H7N9 in Human and Avian Cells

Unique and Specific m6A RNA Methylation in Mouse Embryonic and Postnatal Cerebral Cortices

The Hippo Pathway and Viral Infections

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