title: Interleukin-27 treated human macrophages induce the expression of novel microRNAs which may mediate anti-viral properties.
abstract: Interleukin-27 (IL-27) is a pleiotropic cytokine which plays important and diverse roles in the immune system. We have previously demonstrated that IL-27 induces potent anti-viral effects against HIV-1, HIV-2, SIV, HSV-2, KSHV and influenza viruses in macrophages. This induction occurred in an interferon (IFN) independent manner and involved down regulation of SPTBN1. MicroRNAs (miRNAs) are critical regulators of mRNA translation and turnover. There have been reports that some miRNAs inhibit viral replication. In this study, we hypothesized that IL-27 could induce the expression of novel miRNAs in macrophages which may have functional relevance in terms of anti-viral activity and primary monocytes were differentiated into macrophages using either M-CSF (M-Mac) or a combination of M-CSF and IL-27 (I-Mac) for seven days. Following this, total RNA was extracted from these cells and deep sequencing was performed, in parallel with gene expression microarrays. Using the novel miRNA discovery software, miRDeep, seven novel miRNAs were discovered in these macrophages. Four of which were preferentially expressed in I-Mac (miR-SX1, -SX2, -SX3 and -SX6) whilst three were detected in both M-Mac and I-Mac (miR-SX4, -SX5 and -SX7). The expression of six of the seven novel miRNAs was highly correlated with qRT-PCR using specific primer/probes designed for the novel miRNAs. Gene expression microarray further demonstrated that a number of genes were potentially targeted by these differentially expressed novel miRNAs. Finally, several of these novel miRNAs (miR-SX1, -SX4, -SX5, -SX6 and -SX7) were shown to target the open reading frames of a number of viruses (including HSV-1, HSV-2 and HHV-8) which may partially explain the anti-viral properties observed.
authors.affiliation: Applied and Developmental Research Directorate, Science Application International Corporation (SAIC)-Frederick, Inc., Frederick National Laboratory for Cancer Research (FNLCR), Frederick, MD 21702, USA.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Swaminathan
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Hu
authors.forename: Xin
authors.initials: X
authors.lastname: Zheng
authors.forename: Yuliya
authors.initials: Y
authors.lastname: Kriga
authors.forename: Jyoti
authors.initials: J
authors.lastname: Shetty
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Zhao
authors.forename: Robert
authors.initials: R
authors.lastname: Stephens
authors.forename: Bao
authors.initials: B
authors.lastname: Tran
authors.forename: Michael W
authors.initials: MW
authors.lastname: Baseler
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.forename: Richard A
authors.initials: RA
authors.lastname: Lempicki
authors.forename: Dawei
authors.initials: D
authors.lastname: Huang
authors.forename: H Clifford
authors.initials: HC
authors.lastname: Lane
authors.forename: Tomozumi
authors.initials: T
authors.lastname: Imamichi
mesh_terms: D000998:Antiviral Agents / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D006566:Herpesviridae Infections / Q000188:drug therapy / Q000378:metabolism; D018259:Herpesvirus 1, Human / Q000187:drug effects / Q000235:genetics; D018258:Herpesvirus 2, Human / Q000187:drug effects / Q000235:genetics; D019288:Herpesvirus 8, Human / Q000187:drug effects / Q000235:genetics; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D007378:Interleukins / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000821:virology; D035683:MicroRNAs / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology; D009690:Nucleic Acid Conformation; D020411:Oligonucleotide Array Sequence Analysis; D016366:Open Reading Frames; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D000998:Antiviral Agents; D007378:Interleukins; D035683:MicroRNAs; D012333:RNA, Messenger
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