Anti-HIV type 1 Tat Polyclonal antibody

HIV-1 Tat protein is an important pathogenic factor in HIV1-associated neurological diseases. One hallmark of HIV-1 infection of the central nervous system (CNS) is astrocytosis, which is characterized by elevated glial fibrillary acidic protein (GFAP) expression in astrocytes. We have shown that Tat activates GFAP expression in astrocytes [Zhou et al., (2004) Mol Cell Neurosci 27:296-305] and that GFAP is an important regulator of Tat neurotoxicity [Zou et al., (2007) Am J Pathol 171:1293-1935]. However, the underlying mechanisms for Tat-mediated GFAP up-regulation are not understood. In this study, we reported concurrent upregulation of adenovirus Ela-associated 300 kDa protein p300 and GFAP in Tat-expressing human astroytoma cells and primary astrocytes. We showed that p300 was indeed induced by Tat expression and HIV-1 infection and that the induction occurred at the transcriptional level through the cis-acting elements of early growth response 1 (egr-1) within its promoter. Using siRNA, we further showed that p300 regulated both constitutive and Tat-mediated GFAP expression. Moreover, we showed that ectopic expression of p300 potentiated Tat transactivation activity and increased proliferation of HIV-1-infected astrocytes, but had little effect on HIV-1 replication in these cells. Taken together, these results demonstrate for the first time that Tat is a positive regulator of p300 expression, which in turn regulates GFAP expression, and suggest that the Tat-Egr-1p300-GFAP axis likely contributes to Tat neurotoxicity and predisposes astrocytes to be an HIV-1 sanctuary in the CNS. (C) 2010 Wiley-Liss, Inc.

The potent antiviral effect of double stranded RNA, such as the mismatched poly(I).poly(C12U) [Ampligen], 2',3'-dideoxy-3'-fluorothymidine (FddThd) and antisense oligodeoxynucleotides (ODN) has been established in in vitro systems using cells infected with the human immunodeficiency virus type 1 (HIV-1). We report here that the immunomodulator poly(I).poly(C12U) interacts synergistically with (1) the reverse transcriptase inhibitor FddThd (FIC value: 0.43), (2) the modified (5'- and 3'-end capped thioates) antisense ODN-4 directed against the splice acceptor site of the HIV-1/tat gene (FIC value: 0.66) and (3) also with pyronin Y, a compound which prevents binding of HIV-1 Rev protein to the HIV-1 RRE element. These data suggest that combinations of poly(I)-poly(C12U), a stimulator of the natural antiviral protection system of the cells, with compounds targeting HIV1-specific processes should be considered as candidate treatments of AIDS patients.