HIV-Tat regulates macrophage gene expression in the context of neuroAIDS
| Autor: | Jorge Eduardo Fajardo, Joan W. Berman, Andras Fiser, Lillie Lopez, Loreto Carvallo, Matías Jaureguiberry-Bravo |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
RNA viruses Central Nervous System Chemokine AIDS Dementia Complex Cellular differentiation lcsh:Medicine Gene Expression Pathology and Laboratory Medicine Biochemistry Nervous System Transactivation White Blood Cells Immunodeficiency Viruses Animal Cells Gene expression Medicine and Health Sciences Amino Acids lcsh:Science Regulation of gene expression Multidisciplinary biology Organic Compounds virus diseases Complement C5 Cell Differentiation 3. Good health Chemistry medicine.anatomical_structure Medical Microbiology Viral Pathogens Lentivirus Viruses Physical Sciences Infectious diseases tat Gene Products Human Immunodeficiency Virus Cellular Types Pathogens Basic Amino Acids Anatomy Research Article HIV infections Immune Cells Immunology Nerve Tissue Proteins Viral diseases Microbiology Virus Cell Line 03 medical and health sciences Retroviruses DNA-binding proteins medicine Genetics Humans Gene Regulation Receptors Cytokine Microbial Pathogens Adaptor Proteins Signal Transducing Blood Cells Monocyte Macrophages Lysine Brain-Derived Neurotrophic Factor lcsh:R Organic Chemistry Organisms Chemical Compounds Biology and Life Sciences HIV Proteins Cell Biology biology.organism_classification Virology Regulatory Proteins 030104 developmental biology Amino Acid Substitution Gene Expression Regulation biology.protein lcsh:Q Transcription Factors |
| Zdroj: | PLoS ONE PLoS ONE, Vol 12, Iss 6, p e0179882 (2017) |
| ISSN: | 1932-6203 |
| Popis: | Despite the success of cART, greater than 50% of HIV infected people develop cognitive and motor deficits termed HIV-associated neurocognitive disorders (HAND). Macrophages are the major cell type infected in the CNS. Unlike for T cells, the virus does not kill macrophages and these long-lived cells may become HIV reservoirs in the brain. They produce cytokines/chemokines and viral proteins that promote inflammation and neuronal damage, playing a key role in HIV neuropathogenesis. HIV Tat is the transactivator of transcription that is essential for replication and transcriptional regulation of the virus and is the first protein to be produced after HIV infection. Even with successful cART, Tat is produced by infected cells. In this study we examined the role of the HIV Tat protein in the regulation of gene expression in human macrophages. Using THP-1 cells, a human monocyte/macrophage cell line, and their infection with lentivirus, we generated stable cell lines that express Tat-Flag. We performed ChIP-seq analysis of these cells and found 66 association sites of Tat in promoter or coding regions. Among these are C5, CRLF2/TSLPR, BDNF, and APBA1/Mint1, genes associated with inflammation/damage. We confirmed the association of Tat with these sequences by ChIP assay and expression of these genes in our THP-1 cell lines by qRT-PCR. We found that HIV Tat increased expression of C5, APBA1, and BDNF, and decreased CRLF2. The K50A Tat-mutation dysregulated expression of these genes without affecting the binding of the Tat complex to their gene sequences. Our data suggest that HIV Tat, produced by macrophage HIV reservoirs in the brain despite successful cART, contributes to neuropathogenesis in HIV-infected people. |
| Databáze: | OpenAIRE |
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