Human cytomegalovirus latent infection alters the expression of cellular and viral microRNA

Gene. 2014 Feb 25;536(2):272-8. doi: 10.1016/j.gene.2013.12.012. Epub 2013 Dec 18.


Background: MicroRNAs (miRNAs) play important roles in regulating gene expression of plants, animals and viruses. Comprehensive characterization of host and viral miRNA will help uncover the molecular mechanisms that underlie the progression of human cytomegalovirus (HCMV) latent infection. To investigate the miRNA expression profile of HCMV and host cells during latent infection, we performed deep-sequencing analysis of the small RNAs isolated from HCMV-infected and mock-infected human monocytic leukemia cell line, THP-1.

Results: We established a HCMV latent infection cell model using the THP-1 cells. High-throughput sequencing technology was used to sequence small RNA libraries of the HCMV-infected and mock-infected THP-1 and to investigate their small RNA transcriptomes. We found eight miRNAs including miR-US25-1, miR-US25-2-5p and miR-UL112 that were expressed by HCMV during latent infection. The expressions of the host miRNAs were also affected by HCMV latent infection. At least 49 cellular miRNAs were differentially expressed: 39 were up-regulated and 10 were down-regulated upon HCMV latent infection. The expression of the human miRNA hsa-miR-124-3p was significantly up-regulated in the HCMV latent infection library. In addition, we found 14 cellular novel miRNAs in the HCMV-infected and mock-infected THP-1 libraries. Functional annotation of the target genes of the differentially expressed miRNAs suggested that the majority of the genes are involved in melanogenesis, pathways in cancer, endocytosis and wnt signaling pathway.

Conclusions: The small RNA transcriptomes obtained in this study demonstrate the usefulness of the deep-sequencing combined with bioinformatics approach in understanding of the expression and function of host and viral small RNAs in HCMV latent infection. This approach can also be applied to the study of other kinds of viruses.

Keywords: 3′ UTR; 3′ untranslated regions; AIDS; Acquired Immune Deficiency Syndrome; C/EBPα; CCAAT/enhancer-binding protein α; CTLs; DAVID; Deep-sequencing; Differentially expression; EBV; ER; ERAP; Epstein–Barr virus; FBS; HCMV; HCMV IL-10; HEL; HSV-1; Human cytomegalovirus; Human embryonic lung; IE; KEGG; KSHV; Kaposi's sarcoma-associated herpesvirus; Kyoto encyclopedia of Genes and Genomes; LATs; LAcmvIL-10; LUNA; Latent infection; MAPKs; MICB; MOI; MiRNA; RT-PCR; TBE; THP-1; The Database for Annotation, Visualization and Integrated Discovery; UCSC; University of California, Santa Cruz; cytotoxic T lymphocytes; endoplasmic reticulum; endoplasmic reticulum associated aminopeptidase; fetal bovine serum; herpes simplex virus 1; human cytomegalovirus; human monocytic leukemia cell line; immediate early; latency unique nuclear antigen; latency-associated cmvIL-10; latency-associated transcripts; mRNAs; mTOR; major histocompatibility complex class 1-related chain B; mammalian target of rapamycin; messenger RNAs; miRNAs; microRNAs; mitogen-activated protein kinase; multiplicity of infection; nt; nucleotides; qPCR; quantitative real-time PCR; reverse transcriptase PCR; smRNA; small RNA; small nuclear RNA; snRNA; tris–borate-EDTA; vIL-10.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Cell Line, Tumor
  • Cytomegalovirus / genetics*
  • Cytomegalovirus Infections / genetics*
  • Cytomegalovirus Infections / virology
  • Gene Expression / genetics*
  • Humans
  • Leukemia, Myeloid / genetics
  • Leukemia, Myeloid / virology
  • MicroRNAs / genetics*
  • Transcriptome / genetics
  • Virus Latency / genetics*


  • MicroRNAs