Abstract:
The human astrocyte can be infected with HIV-1 both in vivo and in vitro. However, p24 production is low as compared to that in the macrophage or lymphocyte. Limited viral entry and a subsequent limit in the number of infected cells has been demonstrated to contribute to low p24 production from astrocytes. Yet even when this limitation is overcome, p24 production remains relatively low. We are examining the possibility that p24 production is further limited because of an insufficiency of intracellular factors which are required for a productive infection. NF-kB is one factor which is increased in cells which have a productive infection as compared to the astrocyte. NF-kB has effects at the level of the viral LTR and may also increase expression of cofactors for Rev (G. Nabel, personal communication). We demonstrate that there is little binding of this transcription factor to its consensus sequence in the unstimulated astrocyte as compared to that in the B cell and that increased p24 expression from the astrocyte in response to either transfection or stimuli such as PMA or TNF-alpha is associated with an increase in binding of NF-kB to its consensus sequence. We also demonstrate that stimuli which are associated with both an increase in NF-kB and an increase in p24 are associated with an increase in the supershift of a Rev/RRE complex by astrocyte nuclear proteins. We suggest that in vitro p24 production may be limited in the astrocyte because of an insufficiency of required intracellular factors such as NF-kB that in vivo, because of stimuli that increase NF-kB such as opportunistic infections and elevations in TNF-alpha, this cell type may serve as a viral reservoir.
Keywords: Astrocytes/METABOLISM/*VIROLOGY Biological Factors/*PHYSIOLOGY Gene Products, rev/METABOLISM Human HIV Core Protein p24/BIOSYNTHESIS HIV Enhancer HIV Long Terminal Repeat HIV-1/*PHYSIOLOGY NF-kappa B/BIOSYNTHESIS Protein Binding Tetradecanoylphorbol Acetate/PHARMACOLOGY Transfection Tumor Necrosis Factor/PHARMACOLOGY *Virus Latency ABSTRACT 951230
M95C3052
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