Human Cytomegalovirus Influences Host circRNA Transcriptions during Productive Infection
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RESEARCH ARTICLE
Human Cytomegalovirus Influences Host circRNA Transcriptions during Productive Infection Jingui Deng1,2 • Yujing Huang1 Yibo Li3,4 • Qiang Ruan1
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Qing Wang1 • Jianming Li1 • Yanping Ma1 • Ying Qi1 • Zhongyang Liu1
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Received: 26 April 2020 / Accepted: 8 July 2020 Ó Wuhan Institute of Virology, CAS 2020
Abstract Human cytomegalovirus (HCMV) is a double-strand DNA virus widely infected in human. Circular RNAs (circRNAs) are non-coding RNAs with most functions of which keep unknown, and the effects of HCMV productive infection on host circRNA transcriptions remain unclear. In this study, we profiled 283 host circRNAs that significantly altered by HCMV productive infection in human embryonic lung fibroblasts (HELF) by RNA deep sequencing and bioinformatics analysis. Among these, circSP100, circMAP3K1, circPLEKHM1, and circTRIO were validated for their transcriptions and sequences. Furthermore, characteristics of circSP100 were investigated by RT-qPCR and northern blot. It was implied that circSP100 was produced from the sense strand of the SP100 gene containing six exons. Kinetics of circSP100 and SP100 mRNA were significantly different after infection: circSP100 levels increased gradually along with infection, whereas SP100 mRNA levels increased in the beginning and dropped at 24 h post-infection (hpi). Meanwhile, a total number of 257 proteins, including 10 HCMV encoding proteins, were identified potentially binding to cytoplasmic circSP100 by RNA antisense purification (RAP) and mass spectrometry. Enrichment analysis showed these proteins were mainly involved in the spliceosome, protein processing, ribosome, and phagosome pathways, suggesting multiple functions of circSP100 during HCMV infection. Keywords Human cytomegalovirus (HCMV) Productive infection Circular RNA (circRNA) circSP100 Transcription
Introduction
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12250-020-00275-6) contains supplementary material, which is available to authorized users. & Qiang Ruan [email protected] & Yujing Huang [email protected] 1
Virology Laboratory, The Affiliated Shengjing Hospital, China Medical University, Shenyang 110004, China
2
Department of Laboratory, Central Hospital Affiliated to Shenyang Medical College, Shenyang 110024, China
3
Department of Gynecology and Obstetrics, The Affiliated Shengjing Hospital, China Medical University, Shenyang 110004, China
4
Department of Obstetrics, Central Hospital Affiliated to Shenyang Medical College, Shenyang 110024, China
Human cytomegalovirus (HCMV) is a beta-herpesvirus that can infect many kinds of human cells, including fibroblasts, endothelial cells, neuronal cells, monocytes/macrophages, and dendritic cells (Sinzger et al. 2008). HCMV often causes asymptomatic infection in healthy individuals; however, HCMV is a life-threaten pathogen in congenitally infected newborns and immunocompromised populati
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