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HIV-1 regulatory protein tat induces RNA binding proteins in central nervous system cells that associate with the viral trans-acting-response regulatory motif.
J Hum Virol. 1999 Mar-Apr; 2(2):72-80.JH

Abstract

OBJECTIVES

To investigate some of the cellular consequences of HIV-1 Tat expression in human astrocytic cells. This study is based on evidence that cellular factors play a critical role in facilitating transcriptional activation by Tat through its interaction with the trans-acting-response (TAR) RNA element and upstream HIV-1 long terminal repeat (LTR) promoter binding site. STUDY DESIGN-METHODS: Using the previously established astrocytic cell line of human origin stably transfected with Tat cDNA, we analyzed the formation of a nucleoprotein complex consisting of three cellular proteins associated with TAR RNA using ultraviolet (UV) crosslinking and glutathione-S-transferase (GST) pull-down assays.

RESULTS

UV crosslinking experiments reveal that the molecular masses of the proteins range from 50 to 62 kd. Transient transfection studies demonstrate that the presence of these proteins correlates with the ability of Tat to transactivate the HIV-1 LTR in the absence of the trinucleotide bulge, a region within TAR that has been shown to be important for Tat-TAR interaction. A combination of GST pull-down assays and RNA binding studies demonstrates that the 50-kd protein interacts with both Tat and TAR and is likely to be NF-kappa B p50.

CONCLUSIONS

Taken together, these data suggest that in the absence of a functional Tat binding site such as TAR (which tethers the viral protein to the RNA), cellular protein NF-kappa B p50 may be able to bring Tat into the RNA binding complex Tat has been shown to activate expression of a variety of cellular genes that may not contain a binding site for Tat but do contain binding sites for NF-kappa B family members. The results presented in this study may be relevant for Tat-mediated transactivation of cellular as well as viral genes, both of which might contribute to the central nervous system damage associated with HIV-1 infection.

Authors+Show Affiliations

Department of Neurology, MCP Hahnemann University, Philadelphia, Pennsylvania, USA. Shohreh.Amini@Drexel.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

10225209

Citation

Kundu, M, et al. "HIV-1 Regulatory Protein Tat Induces RNA Binding Proteins in Central Nervous System Cells That Associate With the Viral Trans-acting-response Regulatory Motif." Journal of Human Virology, vol. 2, no. 2, 1999, pp. 72-80.
Kundu M, Ansari SA, Chepenik LG, et al. HIV-1 regulatory protein tat induces RNA binding proteins in central nervous system cells that associate with the viral trans-acting-response regulatory motif. J Hum Virol. 1999;2(2):72-80.
Kundu, M., Ansari, S. A., Chepenik, L. G., Pomerantz, R. J., Khalili, K., Rappaport, J., & Amini, S. (1999). HIV-1 regulatory protein tat induces RNA binding proteins in central nervous system cells that associate with the viral trans-acting-response regulatory motif. Journal of Human Virology, 2(2), 72-80.
Kundu M, et al. HIV-1 Regulatory Protein Tat Induces RNA Binding Proteins in Central Nervous System Cells That Associate With the Viral Trans-acting-response Regulatory Motif. J Hum Virol. 1999;2(2):72-80. PubMed PMID: 10225209.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - HIV-1 regulatory protein tat induces RNA binding proteins in central nervous system cells that associate with the viral trans-acting-response regulatory motif. AU - Kundu,M, AU - Ansari,S A, AU - Chepenik,L G, AU - Pomerantz,R J, AU - Khalili,K, AU - Rappaport,J, AU - Amini,S, PY - 1999/5/4/pubmed PY - 1999/5/4/medline PY - 1999/5/4/entrez SP - 72 EP - 80 JF - Journal of human virology JO - J. Hum. Virol. VL - 2 IS - 2 N2 - OBJECTIVES: To investigate some of the cellular consequences of HIV-1 Tat expression in human astrocytic cells. This study is based on evidence that cellular factors play a critical role in facilitating transcriptional activation by Tat through its interaction with the trans-acting-response (TAR) RNA element and upstream HIV-1 long terminal repeat (LTR) promoter binding site. STUDY DESIGN-METHODS: Using the previously established astrocytic cell line of human origin stably transfected with Tat cDNA, we analyzed the formation of a nucleoprotein complex consisting of three cellular proteins associated with TAR RNA using ultraviolet (UV) crosslinking and glutathione-S-transferase (GST) pull-down assays. RESULTS: UV crosslinking experiments reveal that the molecular masses of the proteins range from 50 to 62 kd. Transient transfection studies demonstrate that the presence of these proteins correlates with the ability of Tat to transactivate the HIV-1 LTR in the absence of the trinucleotide bulge, a region within TAR that has been shown to be important for Tat-TAR interaction. A combination of GST pull-down assays and RNA binding studies demonstrates that the 50-kd protein interacts with both Tat and TAR and is likely to be NF-kappa B p50. CONCLUSIONS: Taken together, these data suggest that in the absence of a functional Tat binding site such as TAR (which tethers the viral protein to the RNA), cellular protein NF-kappa B p50 may be able to bring Tat into the RNA binding complex Tat has been shown to activate expression of a variety of cellular genes that may not contain a binding site for Tat but do contain binding sites for NF-kappa B family members. The results presented in this study may be relevant for Tat-mediated transactivation of cellular as well as viral genes, both of which might contribute to the central nervous system damage associated with HIV-1 infection. SN - 1090-9508 UR - https://www.unboundmedicine.com/medline/citation/10225209/HIV_1_regulatory_protein_tat_induces_RNA_binding_proteins_in_central_nervous_system_cells_that_associate_with_the_viral_trans_acting_response_regulatory_motif_ L2 - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=linkout&SEARCH=10225209.ui DB - PRIME DP - Unbound Medicine ER -