Among candidate antigens for human immunodeficiency virus (HIV) prophylactic vaccines, the regulatory protein Tat is a critical early target, but has a potential for immune suppression. Adenovirus (Ad) recombinants encoding wild-type HIV Tat (Tat-wt) and a transdominant negative mutant HIV Tat (Tat22) were constructed and administered to mice separately or together with Ad-SIVgag. Immunogenicit...

A large number of multicomponent vaccine candidates are currently in clinical evaluation, many of which also include the HIV-1 Tat protein, an important regulatory protein of the virus. However, whether Tat, a known immune effector molecule with a well-conserved sequence among different HIV subtypes, affects the immune response to a coimmunogen is not well understood. In this study, using a bic...

Human immunodeficiency virus type 1 (HIV-1) transcription relies on its transactivating Tat protein. Although devoid of a signal sequence, Tat is released by infected cells and secreted Tat can affect uninfected cells, thereby contributing to HIV-1 pathogenesis. The mechanism and the efficiency of Tat export remained to be documented. Here, we show that, in HIV-1-infected primary CD4(+) T-cells...

Cardiac effects of human immunodeficiency virus (HIV) transactivator (Tat) are unclear, but Tat decreases liver glutathione (an important mitochondrial antioxidant) when ubiquitously expressed in transgenic mice (TG). With an alpha-myosin heavy chain promoter, Tat was selectively targeted to murine cardiac myocytes. One high-expression hemizygous ((+/-)Tat(high); 12 copies) and two low-expressi...

We investigated the effects of the human immunodeficiency virus-1 transactivator of transcription (Tat) on the release of norepinephrine (NE) from human and rat brain synaptosomes. Tat could not evoke directly release of [3H]NE. In the presence of Tat (1 nM), N-methyl-D-aspartate (NMDA) concentrations unable to release (human synaptosomes) or slightly releasing (rat synaptosomes) [3H]NE became ...

Tat protein, a transactivating factor of the human immunodeficiency virus type I, acts also as an extracellular molecule. Heparin affects the bioavailability and biological activity of extracellular Tat (Rusnati, M., Coltrini, D., Oreste, P., Zoppetti, G., Albini, A., Noonan, D., D'Adda di Fagagna, F., Giacca, M., and Presta, M. (1997) J. Biol. Chem. 272, 11313-11320). Here, a series of homogen...

OBJECTIVE To elucidate the effects of human keratinocyte-derived HaCaT cells (HIV-TAT) protein transduction domains (PTD) coupled heme oxygenase-1 (HO-1) fusion protein (TAT-HO-1) on radiation-induced human keratinocyte-derived HaCaT cells. METHODS This study was conducted between May 2010 and February 2013 in the School of Radiation Medicine and Protection, Soochow University, Suzhou, China....

Clostridium botulinum type A (BoNT/A) produces a neurotoxin recently found to be useful as an injectable drug for the treatment of abnormal muscle contractions. The catalytic domain of this toxin which is responsible for the main toxin activity is a zinc metalloprotease that inhibits the release of neurotransmitter mediators in neuromuscular junctions. A cell penetrating cationic peptide, Tat, ...

The mechanism of Tat transactivation was studied by treating cell lines containing Tat-defective viruses with purified Tat protein. These cell lines constitutively produce very low levels of virus in the absence of Tat, as measured by p24 antigen levels. Virus production can be increased greater than 30,000-fold by adding exogenous Tat. Tat addition increases mRNA levels early in the viral life...

HIV-1 trans-acting protein Tat, an essential protein for viral replication, is a key mediator of neurotoxicity. If Tat oxidant injury and neurotoxicity have been described, consequent neuroinflammation is less understood. Rat caudate-putamens (CPs) were challenged with Tat, with or without prior rSV40-delivered superoxide dismutase or glutathione peroxidase. Tat injection caused oxidative stres...