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Block of Tat-mediated transactivation of tumor necrosis factor beta gene expression by polymeric-TAR decoys.
Virology. 1996 Aug 01; 222(1):252-6.V

Abstract

The tat gene product (Tat) of human immunodeficiency virus type 1 (HIV-1) is an early regulatory protein which transactivates HIV-1 gene expression by interacting with the trans-activation response element (TAR) present in the HIV-1 long terminal repeat (LTR). In HIV-1-infected cells Tat can also activate the expression of tumor necrosis factor (TNF). Recent results indicate that essential for this effect is the interaction of Tat with a TAR-like structure present in the TNF beta messenger RNA leader region that closely resembles the TAR of the HIV-LTR. Here we show that because of this similarity of mechanisms, the expression of an RNA species encoding polymeric-TAR sequences and known to inhibit Tat-mediated HIV-1 gene expression also blocks TNF gene expression in response to Tat, but not TNF promoter activation induced by human T cell leukemia/lymphotropic virus type I Tax protein. Since TNF is increased in HIV-1-infected individuals and can activate HIV-1 gene expression or rescue Tat-defective HIV-1 proviruses, activation of TNF by Tat may be part of a complex pathway in which HIV-1 uses its own expression to increase infectivity and to induce disease. This study shows a dual role for the polymeric-TAR construct in inhibiting HIV-1 replication and strengthens the potential use of this protective gene in gene therapy for AIDS.

Authors+Show Affiliations

Howard Hughes Medical Institute, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

8806505

Citation

Brother, M B., et al. "Block of Tat-mediated Transactivation of Tumor Necrosis Factor Beta Gene Expression By polymeric-TAR Decoys." Virology, vol. 222, no. 1, 1996, pp. 252-6.
Brother MB, Chang HK, Lisziewicz J, et al. Block of Tat-mediated transactivation of tumor necrosis factor beta gene expression by polymeric-TAR decoys. Virology. 1996;222(1):252-6.
Brother, M. B., Chang, H. K., Lisziewicz, J., Su, D., Murty, L. C., & Ensoli, B. (1996). Block of Tat-mediated transactivation of tumor necrosis factor beta gene expression by polymeric-TAR decoys. Virology, 222(1), 252-6.
Brother MB, et al. Block of Tat-mediated Transactivation of Tumor Necrosis Factor Beta Gene Expression By polymeric-TAR Decoys. Virology. 1996 Aug 1;222(1):252-6. PubMed PMID: 8806505.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Block of Tat-mediated transactivation of tumor necrosis factor beta gene expression by polymeric-TAR decoys. AU - Brother,M B, AU - Chang,H K, AU - Lisziewicz,J, AU - Su,D, AU - Murty,L C, AU - Ensoli,B, PY - 1996/8/1/pubmed PY - 1996/8/1/medline PY - 1996/8/1/entrez SP - 252 EP - 6 JF - Virology JO - Virology VL - 222 IS - 1 N2 - The tat gene product (Tat) of human immunodeficiency virus type 1 (HIV-1) is an early regulatory protein which transactivates HIV-1 gene expression by interacting with the trans-activation response element (TAR) present in the HIV-1 long terminal repeat (LTR). In HIV-1-infected cells Tat can also activate the expression of tumor necrosis factor (TNF). Recent results indicate that essential for this effect is the interaction of Tat with a TAR-like structure present in the TNF beta messenger RNA leader region that closely resembles the TAR of the HIV-LTR. Here we show that because of this similarity of mechanisms, the expression of an RNA species encoding polymeric-TAR sequences and known to inhibit Tat-mediated HIV-1 gene expression also blocks TNF gene expression in response to Tat, but not TNF promoter activation induced by human T cell leukemia/lymphotropic virus type I Tax protein. Since TNF is increased in HIV-1-infected individuals and can activate HIV-1 gene expression or rescue Tat-defective HIV-1 proviruses, activation of TNF by Tat may be part of a complex pathway in which HIV-1 uses its own expression to increase infectivity and to induce disease. This study shows a dual role for the polymeric-TAR construct in inhibiting HIV-1 replication and strengthens the potential use of this protective gene in gene therapy for AIDS. SN - 0042-6822 UR - https://www.unboundmedicine.com/medline/citation/8806505/Block_of_Tat_mediated_transactivation_of_tumor_necrosis_factor_beta_gene_expression_by_polymeric_TAR_decoys_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0042-6822(96)90416-X DB - PRIME DP - Unbound Medicine ER -