HIV-1 Infection Dysregulates Cell Cycle Regulatory Protein p21 in CD4+ T Cells Through miR-20a and miR-106b Regulation
Autor: | Velpandi Ayyavoo, Allison E. Mancini, Jessica Sparks, Debjani Guha |
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Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Regulation of gene expression Cell Biology Biology Cell cycle Biochemistry CCL5 Cell biology 03 medical and health sciences Interleukin 21 030104 developmental biology 0302 clinical medicine 030220 oncology & carcinogenesis Cytotoxic T cell IL-2 receptor Antigen-presenting cell Molecular Biology Regulator gene |
Zdroj: | Journal of Cellular Biochemistry. 117:1902-1912 |
ISSN: | 0730-2312 |
DOI: | 10.1002/jcb.25489 |
Popis: | Both CD4+ T lymphocytes and macrophages are the major targets of human immunodeficiency virus type 1 (HIV-1); however, they respond differently to HIV-1 infection. We hypothesized that HIV-1 infection alters gene expression in CD4+ T cells and monocyte-derived macrophages (MDMs) in a cell specific manner and microRNAs (miRNAs) in part play a role in cell-specific gene expression. Results indicate that 183 and 31 genes were differentially regulated in HIV-1 infected CD4+ T cells and MDMs, respectively, compared to their mock-infected counterparts. Among the differentially expressed genes, cell cycle regulatory gene, p21 (CDKN1A) was upregulated in virus infected CD4+ T cells both at the mRNA and protein level in CD4+ T cells, whereas no consistent change was observed in MDMs. Productively infected CD4+ T cells express higher amount of p21 compared to bystander cells. In determining the mechanism(s) of cell type specific regulation of p21, we found that the miRNAs miR-106b and miR-20a that target p21 were specifically downregulated in HIV-1 infected CD4+ T cells. Overexpression of these two miRNAs reduced p21 expression significantly in HIV-1 infected CD4+ T cells. These findings provide a potential mechanism, by which, HIV-1 could exploit host cellular machineries to regulate selective gene expression in target cells. J. Cell. Biochem. 117: 1902-1912, 2016. © 2016 Wiley Periodicals, Inc. |
Databáze: | OpenAIRE |
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