A review of HIV-1 Tat protein biological effects

Abstract

The authors have reviewed some biological properties of HIV-1 Tat protein, and have also reported some personal data. This viral regulatory protein is endowed with multifunctional activities, acting as an endogenous factor in the infected cells and exogenously, on those uninfected. In particular, Tat-induced proliferation and differentiation of HIV target cells which promotes viral infection, is discussed in this review. However, exogenous Tat protein can sometimes also produce, directly or indirectly, damaging effects in different organs and host systems, such as myocardium, kidney, liver and central nervous system (CNS). For example some data also demonstrate an increase in the apoptotic index induced by Tat at various levels, including the immune system. The effective role of HIV-1 Tat protein in promoting viral replication and its high immunogenicity suggest useful employment of this protein for therapeutic or preventive vaccine preparations.

Lipodystrophy in HIV 1-infected patients: lessons for obesity research

“…73,74 Although no studies have 73,75 Recently available transgenic mice expressing the HIV-1 Vpr protein in adipose tissues and in the liver show altered systemic lipid metabolism. 76 Vpr is also a known inducer of apoptosis through activation of the mitochondrial permeability transition pore (MPTP) 77 and therefore may contribute to adipocyte apoptosis in HALS, although this issue has not yet been addressed in adipose cells.…”

Cannabinoid Inhibition of Macrophage Migration to the Trans-Activating (Tat) Protein of HIV-1 Is Linked to the CB2Cannabinoid Receptor

“…Once infected, these cells produce and secrete chemokines, cytokines, and other toxic factors, including the viral trans-activating protein (Tat) and HIV glycoprotein 120 (Gp120) that collectively play critical roles in the progression of HIV infection by directly altering immune homeostasis. HIV-1 Tat (trans-activating factor) is a regulatory protein that is indispensible for viral replication and gene expression (reviewed in Pugliese et al, 2005). This protein, once secreted, is highly immunogenic and induces the production of proinflammatory cytokines and chemokines in astrocytes (El-Hage et al, 2006), monocytes (Lafrenie et al, 1997), microglia (reviewed in Minghetti et al, 2004), and T lymphocytes (Kim et al, 2004).…”

Functions of Tat: the versatile protein of human immunodeficiency virus type 1

“…The role of Tat in apoptosis becomes more complicated in the CNS. Despite the adverse effects of Tat protein on the CNS, it has been shown that Tat binds to Bcl-X L , an antiapoptotic member of the Bcl-2 family, and forms a complex capable of inhibiting apoptosis in neuronal cells both in vitro and in vivo (Pugliese et al, 2005). Cantaluppi et al (2001) have shown that Tat, in a dosedependent manner, protects Kaposi's sarcoma (KS) cell lines and human umbilical vein endothelial cells from apoptosis induced by vincristine or serum starvation, respectively.…”

“…1). The first exon encodes the first 72 aa (Pugliese et al, 2005;Schwarze et al, 1999). Due to the variable length of Tat, its weight varies from 14 to 16 kDa.…”

“…This is a post-transcriptional modification that consists of cutting of the tat mRNA and removal of unnecessary sequences. The process is followed by the joining together of nucleic acid sequences (FanalesBelasio et al, 2009;Pugliese et al, 2005).…”