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PMID: 8419644 Published · ppublish English Journal Article

Human immunodeficiency viruses containing heterologous enhancer/promoters are replication competent and exhibit different lymphocyte tropisms.

Journal of virology ·Vol. 67 ·No. 2 ·1993-02-00 ·Pages 743-52

Chang LJ, McNulty E, Martin M

Abstract

The human immunodeficiency virus (HIV) type 1 long terminal repeat (LTR) contains binding sites for nuclear factor kappa B (NF-kappa B) and the constitutively expressed transcription factor Sp1, both of which are highly conserved in HIV and simian immunodeficiency virus isolates. To delineate the effects of these motifs on the replicative capacity of HIV and to explore the possibility of extending the virus host range, known heterologous enhancer/promoters were inserted into the HIV-1 LTR in place of the NF-kappa B and Sp1 binding sites. The effects of these substitutions on viral replication in transfected HeLa cells and on HIV infection of human peripheral blood lymphocytes or continuous T-leukemia cell lines were evaluated. HIVs in which the NF-kappa B/Sp1 enhancer plus the downstream TATA element were replaced with heterologous enhancer/promoters were also constructed. Viruses containing the human cytomegalovirus immediate-early enhancer exhibited infectious kinetics similar to that of wild-type HIV in activated human peripheral blood lymphocytes and AA2 cells but replicated less efficiently in H9 and CEM cells. These studies indicate that heterologous enhancer elements are capable of restoring Tat responsiveness to the HIV LTR in the context of directing reporter gene expression as well as in the production of infectious progeny virions.

MeSH Terms
Base Sequence Chloramphenicol O-Acetyltransferase/genetics DNA, Recombinant/genetics Enhancer Elements, Genetic/genetics Gene Expression Regulation, Viral/genetics Gene Products, tat/biosynthesis Genes, tat/genetics Genome, Viral HIV Long Terminal Repeat/genetics HIV-1/genetics,growth & development Humans Lymphocytes/microbiology Molecular Sequence Data NF-kappa B/metabolism Promoter Regions, Genetic/genetics Proviruses/genetics Sp1 Transcription Factor/metabolism TATA Box Transcriptional Activation/genetics Tumor Cells, Cultured Virus Replication tat Gene Products, Human Immunodeficiency Virus
Chemicals
DNA, Recombinant Gene Products, tat NF-kappa B Sp1 Transcription Factor tat Gene Products, Human Immunodeficiency Virus Chloramphenicol O-Acetyltransferase
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Chang L J
Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892.
McNulty E
Martin M
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.67.2.743-752.1993
Published
1993-02-00
Pages
743-52
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC237426
Subset
IM
External Links
PubMed source DOI: 10.1128/JVI.67.2.743-752.1993 PMC Full Text View journal details
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