MicroRNA-mediated regulation of p21 and TASK1 cellular restriction factors enhances HIV-1 infection
| Autor: | Eytan Herzig, Amnon Hizi, Shira Modai, Ofer Isakov, Luba Farberov, Noam Shomron |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Cyclin-Dependent Kinase Inhibitor p21
Cyclin-dependent kinase inhibitor T-Lymphocytes Molecular Sequence Data Down-Regulation HIV Infections Nerve Tissue Proteins Biology Virus Replication TASK1 Potassium Channels Tandem Pore Domain Downregulation and upregulation microRNA Gene silencing Humans RNA Messenger Gene miRNA Regulation of gene expression Cellular restriction factor Base Sequence HEK 293 cells Cell Biology Human immunodeficiency virus-type 1 Virology Cell biology Up-Regulation MicroRNAs HEK293 Cells Viral replication Gene Expression Regulation Cell culture HIV-1 Research Article |
| Zdroj: | Journal of Cell Science |
| ISSN: | 1477-9137 0021-9533 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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