Abstract
Human cytomegalovirus (HCMV) is an opportunistic prototypic beta-herpesvirus that can cause severe and even fatal diseases in immune-naive newborns and immunocompromised adults. Host-virus interactions occurring at the transcriptional and posttranscriptional levels are critical for establishing an HCMV latent or lytic infection, but the mechanisms remain poorly understood. Herein, we investigated the expression of circRNAs in human leukemia monocytes (THP-1 cells) latently infected with HCMV and explored the diagnostic value of circRNAs in children with HCMV infection. A total of 2,110 and 1,912 circRNAs were identified in mock-infected and HCMV latent-infected THP-1 cells, respectively. Of these, we identified 1,421 differently expressed circRNAs, of which 650 were upregulated and 771 were downregulated. The host genes corresponding to the differentially expressed circRNAs were mainly involved in the regulation of host cell secretion pathways, cell cycle, and cell apoptosis. The differentially expressed circRNAs had binding sites for microRNAs, suggesting an important role in the mechanism of HCMV latent infection. Furthermore, a clinical analysis showed that the expression levels of hsa_circ_0001445 and hsa_circ_0001206 were statistically significantly different in HCMV-infected patients vs. normal controls, suggesting that these circRNAs could potentially serve as biomarkers of HCMV-infection.
Highlights
Human cytomegalovirus (HCMV) is an opportunistic prototypic beta-herpesvirus that is widespread in the human population and can lead to severe and even fatal diseases in immune-naive newborns and immunocompromised adults [12, 32, 45]
Validation of the differential expression of circRNAs identified by RNA sequencing (RNA-Seq) analysis was performed with quantitative real-time PCR in 11 randomly selected RNA samples
We found that there was a significant correlation between the quantitative real-time PCR (qPCR) data and the RNASeq data (Pearson correlation coefficient ϭ 0.88; P Ͻ 0.001) (Fig. 1C)
Summary
Human cytomegalovirus (HCMV) is an opportunistic prototypic beta-herpesvirus that is widespread in the human population and can lead to severe and even fatal diseases in immune-naive newborns and immunocompromised adults [12, 32, 45]. The microRNAs encoded by HCMV target and suppress different molecules in the human immune system by means of transcriptional and epigenetic regulation to achieve immune escape, so as to provide favorable conditions for HCMV latent infection [29, 43, 44]. The transcriptional and epigenetic mechanisms of microRNAs in an HCMV latent infection need to be studied in detail. We used a high-throughput sequencing (HTS) technology to obtain the expression profile of circRNA in HCMV latent-infected vs mock-infected THP-1 cells and performed bioinformatics and a clinical analysis of the differentially expressed circRNAs to provide insights into the mechanism of HCMV infection
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