Abstract
Little is known about the particular changes of N6-methyladenosine (m6A) RNA methylation in enterovirus (EV) infection among children with neurologic symptoms. Here, we determined the characterization of EV associated m6A RNA methylation in this population. A prospective cohort study was conducted from 2018/2 to 2019/12 at the Guangzhou Women and Children’s Medical Center. We included EV infected children with and without neurological symptoms. High-throughput m(6)A-RNA immunoprecipitation sequencing (MeRIP-seq) and RNA-seq analysis were used to evaluate the m6A RNA methylation and transcript expression of cerebrospinal fluid samples. The functional annotation and pathways of differentially methylated m6A genes with synchronously differential expression were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Seven patients were enrolled in the control group, and 13 cases were in the neurological symptoms (NS) group. A total of 3472 differentially expressed genes and 957 m6A modified genes were identified. A conjoint analysis of MeRIP-seq and RNA-seq data found 1064 genes with significant changes in both the m6A modifications and mRNA levels. The different m6A RNA methylation was increased in the transcriptome’s CDS regions but decreased in both the 3′UTRs and stop codon among the NS group. Functional annotation like the “oxidative phosphorylation” gene pathway, “Parkinson’s disease” and GO terms like “respiratory electron transport chain,” “cellular metabolic process,” and “oxidation-reduction process” was enriched in symptomatic patients. Our study elucidated the changes of RNA m6A methylation patterns and related cellular functions and signaling pathways in EV patients with neurologic symptoms.
Highlights
Enteroviruses (EV) are common pathogens that causes an array of diseases, especially in neonates
The aim of our study was to explore the underlying mechanism of EV related neurological damage by using RNA-sequencing technology to profile the transcriptome alterations of m6A RNA methylation in CSF samples of simple EV infected children with and without neurologic symptoms
We previously found that somnolence in EV patients was correlated with high mortality (Yang et al, 2018)
Summary
Enteroviruses (EV) are common pathogens that causes an array of diseases, especially in neonates. This includes hand-foot and mouth disease (HFMD), aseptic meningitis, encephalitis, acute flaccid paralysis, and acute flaccid myelitis (Gonzalez et al, 2019). It has several genotypes, among which, EV-A71, CVA6 and CV-A16 have caused large epidemics in Asia since 1997 (Lee et al, 2014; Wang et al, 2017; Huang et al, 2018). Enteroviruses infection is known to cause thalamus and medulla oblongata damage, induces a persisting neurological sequelae or even death (Gonzalez et al, 2019). Our understanding of the molecular mechanisms involved in EV infections has increased dramatically in the past few years, the exact mechanisms of enterovirus infection still remain unknown, especially with regards to the pathogenesis of neurologic damage
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