Back to Search
Start Over
miR-190b is markedly upregulated in the intestine in response to simian immunodeficiency virus replication and partly regulates myotubularin-related protein-6 expression.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2014 Aug 01; Vol. 193 (3), pp. 1301-13. Date of Electronic Publication: 2014 Jun 30. - Publication Year :
- 2014
-
Abstract
- HIV replication and the cellular micro-RNA (miRNA) machinery interconnect at several posttranscriptional levels. To understand their regulatory role in the intestine, a major site of HIV/SIV replication, dissemination, and CD4(+) T cell depletion, we profiled miRNA expression in colon following SIV infection (10 acute SIV, 5 uninfected). Nine (four up and five down) miRNAs showed statistically significant differential expression. Most notably, miR-190b expression showed high statistical significance (adjusted p = 0.0032), the greatest fold change, and was markedly elevated in colon and jejunum throughout SIV infection. In addition, miR-190b upregulation was detected before peak viral replication and the nadir of CD4(+) T cell depletion predominantly in lamina propria leukocytes. Interestingly non-SIV-infected macaques with diarrhea and colitis failed to upregulate miR-190b, suggesting that its upregulation was neither inflammation nor immune-activation driven. SIV infection of in vitro-cultured CD4(+) T cells and primary intestinal macrophages conclusively identified miR-190b upregulation to be driven in response to viral replication. Further miR-190b expression levels in colon and jejunum positively correlated with tissue viral loads. In contrast, mRNA expression of myotubularin-related protein 6 (MTMR6), a negative regulator of CD4(+) T cell activation/proliferation, significantly decreased in SIV-infected macrophages. Luciferase reporter assays confirmed MTMR6 as a direct miR-190b target. To our knowledge, this is the first report, which describes dysregulated miRNA expression in the intestine, that identifies a potentially significant role for miR-190b in HIV/SIV pathogenesis. More importantly, miR-190b-mediated MTMR6 downregulation suggests an important mechanism that could keep infected cells in an activated state, thereby promoting viral replication. In the future, the mechanisms driving miR-190b upregulation including other cellular processes it regulates in SIV-infected cells need determination.<br /> (Copyright © 2014 by The American Association of Immunologists, Inc.)
- Subjects :
- Animals
CD4-Positive T-Lymphocytes immunology
CD4-Positive T-Lymphocytes virology
Colon immunology
Colon metabolism
Colon virology
Down-Regulation genetics
Down-Regulation immunology
Genes, Reporter
Intestinal Mucosa immunology
Intestinal Mucosa virology
Jejunum immunology
Jejunum metabolism
Jejunum virology
Luciferases genetics
Macaca mulatta
MicroRNAs biosynthesis
Protein Tyrosine Phosphatases, Non-Receptor biosynthesis
RNA, Viral genetics
RNA, Viral immunology
Retroviruses, Simian immunology
Simian Acquired Immunodeficiency Syndrome immunology
Simian Immunodeficiency Virus immunology
Up-Regulation immunology
Virus Replication immunology
Intestinal Mucosa metabolism
MicroRNAs genetics
Protein Tyrosine Phosphatases, Non-Receptor genetics
Retroviruses, Simian genetics
Simian Acquired Immunodeficiency Syndrome genetics
Simian Immunodeficiency Virus genetics
Up-Regulation genetics
Virus Replication genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 193
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 24981450
- Full Text :
- https://doi.org/10.4049/jimmunol.1303479