Human immunodeficiency virus type 1 clade B and C Tat differentially induce indoleamine 2,3-dioxygenase and serotonin in immature dendritic cells: Implications for neuroAIDS
| Autor: | Madhavan Nair, Thangavel Samikkannu, Nimisha Gandhi, Shailendra K. Saxena, Kurapati V. K. Rao |
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| Rok vydání: | 2010 |
| Předmět: |
Serotonin
AIDS Dementia Complex Blotting Western Gene Expression HIV Infections Cell Separation Cellular and Molecular Neuroscience Transactivation chemistry.chemical_compound Immune system Virology Humans Indoleamine-Pyrrole 2 3 -Dioxygenase Neurovirology Indoleamine 2 3-dioxygenase Kynurenine Serotonin transporter Serotonin Plasma Membrane Transport Proteins Regulation of gene expression biology Reverse Transcriptase Polymerase Chain Reaction Gene Expression Profiling Dendritic Cells Dendritic cell Flow Cytometry Neurology chemistry HIV-1 biology.protein tat Gene Products Human Immunodeficiency Virus Neurology (clinical) |
| Zdroj: | Journal of Neurovirology. 16:255-263 |
| ISSN: | 1538-2443 1355-0284 |
| DOI: | 10.3109/13550284.2010.497809 |
| Popis: | Human immunodeficiency virus type 1 (HIV-1) is commonly associated with immune dysfunctions and the suppression of antigen-presenting cells. This results in immune alterations, which could lead to impaired neuronal functions, such as neuroAIDS. The neurotoxic factor kynurenine (KYN), the ratelimiting enzyme indoleamine 2,3-dioxygenase (IDO), serotonin (5-HT), and serotonin transporter (5-HTT) may play a role in tryptophan deficiency and serotogenic dysfunction in neuroAIDS. HIV-1 transactivator regulatory protein (Tat) is known to play a major role in immune dysfunction. Previous studies suggest that HIV-1 B and C clades differentially manifest neuronal dysfunctions in the infected host. In the present study we examine the effect of HIV-1 B and C clade–derived Tat on IDO and 5-HTT gene and protein expressions by dendritic cells as studied by quantitative polymerase chain reaction (qPCR) and Western blot. In addition, the intracellular IDO expression, IDO enzyme activity, and the levels of 5-HT and KYN were also measured. Results indicate that HIV-1 clade B Tat up-regulates IDO and down-regulates 5-HTT gene and protein expressions. Further, HIV-1 clade B Tat caused a reduction of 5-HT with simultaneous increase in KYN levels as compared to HIV-1 clade C Tat. These studies suggest that HIV-1 clade B and C Tat proteins may play a differential role in the neuropathogenesis of HIV-associated dementia (HAD) or HIV-associated neurocognitive disorder (HAND). Journal of NeuroVirology (2010) 16, 255–263. |
| Databáze: | OpenAIRE |
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