Extracellular HIV-1 Tat Induces Human Beta-Defensin-2 Production Via NF-kappaB/AP-1 Dependent Pathways in Human B Cells

Novel Neuroprotective GSK-3β Inhibitor Restricts Tat-Mediated HIV-1 Replication

“…To date, there are very limited interventions available to prevent HIV-1-associated neurotoxicity or dementia. Although Nef, Rev, and Vpr have been linked to neurotoxicity, the neurotoxic effects of HIV-1 are largely attributed to gp120 and Tat proteins (7,9,10,27,28,(113)(114)(115). Current cART treatment does not block production of early viral proteins, such as Tat, even during successful virus suppression, and thus, extracellular Tat released into the extracellular space can exert neurotoxic effects on bystander cells (116,117).…”

“…A portion of the current research efforts focus on finding novel host-based therapies that can provide viral inhibition in tandem with protection of cells from apoptosis. Cytoprotective effects are desirable in order to protect already depleted cell populations and to counteract detrimental effects of viral proteins, such as Tat and gp120 (Env), which are normally generated during infection (6)(7)(8)(9)(10)(11).…”

Identifying Chemicals with Potential Therapy of HIV Based on Protein-Protein and Protein-Chemical Interaction Network

“…Histone acetyltransferase p300 and SP1 interact with HIV-1 Viral protein-R (Vpr) to mediate Vpr activity in virion assemble, nucleus locating, promoter activation, cell cycle arrest or apoptosis induction [36]. In addition, Histone acetyltransferase p300, GRB2, Polyubiquitin-C, Akt-1, MAPK8 are all involved in the HIV trans- activating protein Tat mediated transactivation of HIV-1 LTR and viral replication, respectively [37], [38], [39], [40], [41]. Several proteins are to function by the similar pathway, such as the NF-κB signaling pathway or JAK-STAT pathway.…”

Toll-like receptor 2-mediated induction of avian β -defensin 9 by Lactobacillus rhamnosus and its cellular components in chicken intestinal epithelial cells

“…MAPK is an essential component of the signal transduction machinery that consists of at least three distinct subfamilies: p38, JNK, and ERK1/2all of which are upstream mediators for AP-1 activation (Kaminska, 2005). Previous studies have indicated that several MAPKs are involved in the signalling cascades leading to expression of defensins upon various stimuli (Gan et al, 2014;Jang et al, 2004;Ju et al, 2012;Kim et al, 2013;Li et al, 2013;Madi et al, 2013). Among these studies, all three main MAPKs, p38, JNK, and ERK1/2, or two of them, were reported to be involved in mediating induction of defensins in response to a variety of stimuli.…”