Abstract
The current AIDS pandemic represents the uneven spread of multiple genetically related subtypes (A to J) of human immunodeficiency virus type 1 (HIV-1). Notably, HIV-1 E in southeast Asia and HIV-1 C in sub-Saharan Africa are expanding faster and are likely of greater global significance than the HIV-1 B subtype prevalent in the United States and Europe. While many studies have focused on genetic variation among structural genes, we chose to conduct a comparative analysis of the long terminal repeats of HIV-1 E and HIV-1 C isolates and report subtype-specific differences in enhancer copy numbers and sequences, as well as divergent activation in response to the cellular transcriptional activators Rel-p65 and NFATc and viral Tat. This study is the first to identify functional distinctions in promoter architecture between HIV-1 subtypes and raises the possibility that regulatory divergence among the subtypes of HIV-1 has occurred. Divergent transcriptional regulation may explain some of the epidemiologically observed differences in transmission and pathogenesis and underscores the need for further comparative analysis of HIV-1 regulation.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Base Sequence
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Binding Sites
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DNA, Viral / genetics
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DNA-Binding Proteins / metabolism
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DNA-Binding Proteins / physiology
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Gene Expression Regulation, Viral
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Gene Products, tat / physiology
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HIV Long Terminal Repeat
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HIV-1 / classification
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HIV-1 / genetics*
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Humans
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Molecular Sequence Data
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NF-kappa B / physiology
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NFATC Transcription Factors
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Nuclear Proteins*
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Phylogeny
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Promoter Regions, Genetic
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Proviruses
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Sequence Alignment
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Sequence Homology, Nucleic Acid
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Transcription Factor RelA
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Transcription Factors / metabolism
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Transcription Factors / physiology
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Transcription, Genetic
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tat Gene Products, Human Immunodeficiency Virus
Substances
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DNA, Viral
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DNA-Binding Proteins
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Gene Products, tat
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NF-kappa B
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NFATC Transcription Factors
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Nuclear Proteins
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Transcription Factor RelA
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Transcription Factors
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tat Gene Products, Human Immunodeficiency Virus
Associated data
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GENBANK/AF023426
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GENBANK/AF023427
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GENBANK/AF023428
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GENBANK/AF023429
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GENBANK/AF023430
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GENBANK/AF023431
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GENBANK/AF023432
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GENBANK/AF023433
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GENBANK/AF023434
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GENBANK/AF023435
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GENBANK/AF023436
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GENBANK/AF023437
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GENBANK/AF023438
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GENBANK/AF023439
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GENBANK/AF023440
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GENBANK/AF023441