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.
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 rate-limiting 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).
Samikkannu
Thangavel
T
Department of Immunology, Institute of NeuroImmune Pharmacology, College of Medicine, Florida International University, Miami, Florida 33199, USA.
Rao
Kurapati V K
KV
Gandhi
Nimisha
N
Saxena
Shailendra K
SK
Nair
Madhavan P N
MP
D015526:AIDS Dementia Complex / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002469:Cell Separation; D003713:Dendritic Cells / Q000378:metabolism* / Q000821:virology; D005434:Flow Cytometry; D015870:Gene Expression; D020869:Gene Expression Profiling; D015658:HIV Infections / Q000276:immunology / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000096:biosynthesis*; D007737:Kynurenine / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012701:Serotonin / Q000096:biosynthesis*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*
D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D054322:tat Gene Products, Human Immunodeficiency Virus; D012701:Serotonin; D007737:Kynurenine