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Abstract

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)

Biography

Shailendra Saxena is a Medical Microbiologist at Centre for Cellular and Molecular Biology (CCMB) in India. The main research interests of his group are to understand the epidemiology and molecular mechanisms of host-defense during human viral infections and to develop new predictive, preventive and therapeutic strategies for them using JEV and HIV as a model. His research work has been published in various high impact factor journals (Science, PNAS) with high citation. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award and named as ?Global Leader in Science? by The Scientist magazine (USA) and ?International Opinion Leader / Expert? involved in the vaccination for JE by IPIC (UK).