Human Cytomegalovirus Influences Host circRNA Transcriptions during Productive Infection

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.