title: MicroRNA-mediated regulation of p21 and TASK1 cellular restriction factors enhances HIV-1 infection.
abstract: MicroRNAs (miRNAs) are short non-coding RNAs that play a central role in the regulation of gene expression by binding to target mRNAs. Several studies have revealed alterations in cellular miRNA profiles following HIV-1 infection, mostly for miRNAs involved in inhibiting viral infection. These miRNA expression modifications might also serve to block the innate HIV-1 inhibition mechanism. As a result, it is expected that during HIV-1 infection miRNAs target genes that hinder or prevent the progression of the HIV-1 replication cycle. One of the major sets of genes known to inhibit the progression of HIV-1 infection are cellular restriction factors. In this study, we identified a direct miRNA target gene that modulates viral spread in T-lymphocytes and HeLa-CCR5 cell lines. Following infection, let-7c, miR-34a or miR-124a were upregulated, and they targeted and downregulated p21 and TASK1 (also known as CDKN1A and KCNK3, respectively) cellular proteins. This eventually led to increased virion release and higher copy number of viral genome transcripts in infected cells. Conversely, by downregulating these miRNAs, we could suppress viral replication and spread. Our data suggest that HIV-1 exploits the host miRNA cellular systems in order to block the innate inhibition mechanism, allowing a more efficient infection process.
authors.affiliation: Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Luba
authors.initials: L
authors.lastname: Farberov
authors.affiliation: Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Eytan
authors.initials: E
authors.lastname: Herzig
authors.affiliation: Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Shira
authors.initials: S
authors.lastname: Modai
authors.affiliation: Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Ofer
authors.initials: O
authors.lastname: Isakov
authors.affiliation: Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Amnon
authors.initials: A
authors.lastname: Hizi
authors.affiliation: Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel nshomron@post.tau.ac.il.
authors.forename: Noam
authors.initials: N
authors.lastname: Shomron
mesh_terms: D001483:Base Sequence; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D015536:Down-Regulation; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D015658:HIV Infections / Q000378:metabolism; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D024683:Potassium Channels, Tandem Pore Domain / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D013601:T-Lymphocytes / Q000821:virology; D015854:Up-Regulation; D014779:Virus Replication
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; C509207:MIRN124 microRNA, human; C522425:MIRN34 microRNA, human; D035683:MicroRNAs; D009419:Nerve Tissue Proteins; D024683:Potassium Channels, Tandem Pore Domain; D012333:RNA, Messenger; C487931:mirnlet7 microRNA, human; C420132:potassium channel subfamily K member 3
keywords: Cellular restriction factor; Cyclin‐dependent kinase inhibitor; Human immunodeficiency virus‐type 1; TASK1; miRNA