title: Human cytomegalovirus latent infection alters the expression of cellular and viral microRNA.
abstract: 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.
authors.affiliation: Department of the Laboratory Medicine, The Second Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China; Jinhua Municipal Central Hospital, Jinhua, Zhejiang, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Fu
authors.affiliation: Department of the Laboratory Medicine, The Second Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of the Laboratory Medicine, The Second Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Qiuju
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Department of the Laboratory Medicine, The Second Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, Zhejiang, China; Key Laboratory of Laboratory Medicine, Ministry of Education, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Peng
authors.affiliation: Hospital of Qingdao University Medical College, Qingdao, Shandong, China.
authors.forename: Kegang
authors.initials: K
authors.lastname: Tian
authors.affiliation: Jinhua Municipal Central Hospital, Jinhua, Zhejiang, China.
authors.forename: Jinhua
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of the Laboratory Medicine, The Second Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China; School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, Zhejiang, China; Key Laboratory of Laboratory Medicine, Ministry of Education, China. Electronic address: jszhengxq@163.com.
authors.forename: Xiaoqun
authors.initials: X
authors.lastname: Zheng
mesh_terms: D002460:Cell Line; D045744:Cell Line, Tumor; D003587:Cytomegalovirus / Q000235:genetics*; D003586:Cytomegalovirus Infections / Q000235:genetics* / Q000821:virology; D015870:Gene Expression / Q000235:genetics*; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics / Q000821:virology; D035683:MicroRNAs / Q000235:genetics*; D059467:Transcriptome / Q000235:genetics; D017735:Virus Latency / Q000235:genetics*
chemical_list: D035683:MicroRNAs
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