Description
Transactivator of transcription (TAT) protein is produced by HIV-1 and is involved in the induction of HIV-associated neurologic disorders (HAND). TAT is a neurotoxin that infects neurons, which HIV itself is unable to do. In neurons, TAT increases the number of inhibitory synapses and decreases the number of excitatory synapses in a Ca2+-dependent manner. TAT also activates microglia and other myeloid cells, disrupting cytokine/chemokine homeostasis and inducing neuroinflammation. This peptide sequence (YGRKKRRQRRR) represents the protein transduction (cell-penetrating) domain of TAT.
References
Hargus NJ, Thayer SA. Human immunodeficiency virus-1 Tat protein increases the number of inhibitory synapses between hippocampal neurons in culture. J Neurosci. 2013 Nov 6;33(45):17908-20. PMID: 24198379.
Bethel-Brown C, Yao H, Callen S, et al. HIV-1 Tat-mediated induction of platelet-derived growth factor in astrocytes: role of early growth response gene 1. J Immunol. 2011 Apr 1;186(7):4119-29. PMID: 21368226.
Lu SM, Tremblay MÈ, King IL, et al. HIV-1 Tat-induced microgliosis and synaptic damage via interactions between peripheral and central myeloid cells. PLoS One. 2011;6(9):e23915. PMID: 21912650.
