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PMID: 1505523 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

TAR-independent transactivation by Tat in cells derived from the CNS: a novel mechanism of HIV-1 gene regulation.

The EMBO journal ·Vol. 11 ·No. 9 ·1992-09-00 ·Pages 3395-403

Taylor JP, Pomerantz R, Bagasra O, Chowdhury M, Rappaport J, Khalili K, Amini S

Abstract

The Tat protein of human immunodeficiency virus type 1 (HIV-1) is essential for productive infection and is a potential target for antiviral therapy. Tat, a potent activator of HIV-1 gene expression, serves to greatly increase the rate of transcription directed by the viral promoter. This induction, which seems to be an important component in the progression of acquired immune deficiency syndrome (AIDS), may be due to increased transcriptional initiation, increased transcriptional elongation, or a combination of these processes. Much attention has been focused on the interaction of Tat with a specific RNA target termed TAR (transactivation responsive) which is present in the leader sequence of all HIV-1 mRNAs. This interaction is believed to be an important component of the mechanism of transactivation. In this report we demonstrate that in certain CNS-derived cells Tat is capable of activating HIV-1 through a TAR-independent pathway. A Tat-responsive element is found upstream within the viral promoter that in glial-derived cell lines allows transactivation in the absence of TAR. Deletion mapping and hybrid promoter constructs demonstrate that the newly identified Tat-responsive element corresponds to a sequence within the viral long terminal repeat (LTR) previously identified as the HIV-1 enhancer, or NF-kappa B domain. DNA band-shift analysis reveals NF-kappa B binding activity in glial cells that differs from that present in T lymphoid cells. Further, we observe that TAR-deleted mutants of HIV-1 demonstrate normal late gene expression in glial cells as evidenced by syncytia formation and production of viral p24 antigen.(ABSTRACT TRUNCATED AT 250 WORDS)

MeSH Terms
Animals Base Sequence Cell Fusion Cell Line Gene Expression Regulation, Viral Gene Products, tat/metabolism HIV-1/genetics Humans Molecular Sequence Data NF-kappa B/metabolism Neuroglia/microbiology Promoter Regions, Genetic/genetics RNA, Viral/metabolism Regulatory Sequences, Nucleic Acid Repetitive Sequences, Nucleic Acid/genetics T-Lymphocytes/microbiology Transcription, Genetic Transcriptional Activation Virus Replication/genetics tat Gene Products, Human Immunodeficiency Virus
Chemicals
Gene Products, tat NF-kappa B RNA, Viral tat Gene Products, Human Immunodeficiency Virus
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Taylor J P
Department of Biochemistry and Molecular Biology, Jefferson Institute of Molecular Medicine, Thomas Jefferson University, Philadelphia, PA 19107.
Pomerantz R
Bagasra O
Chowdhury M
Rappaport J
Khalili K
Amini S
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1992-09-00
Pages
3395-403
Language
English
Region
England
NLM ID
8208664
PMCID
PMC556874
Subset
IM
Grants
NIAID NIH HHS · AI00930 · United States
NIAID NIH HHS · AI28272 · United States
NCI NIH HHS · CA47996 · United States
External Links
PubMed source PMC Full Text View journal details
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