Divergent transcriptional regulation among expanding human immunodeficiency virus type 1 subtypes.
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.
Montano
M A
MA
Harvard AIDS Institute, Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
Novitsky
V A
VA
Blackard
J T
JT
Cho
N L
NL
Katzenstein
D A
DA
Essex
M
M
D001483:Base Sequence; D001665:Binding Sites; D004279:DNA, Viral / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology; D015967:Gene Expression Regulation, Viral; D015696:Gene Products, tat / Q000502:physiology; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000145:classification / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000502:physiology; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D010802:Phylogeny; D011401:Promoter Regions, Genetic; D011533:Proviruses; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid; D051996:Transcription Factor RelA; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology; D014158:Transcription, Genetic; D054322:tat Gene Products, Human Immunodeficiency Virus
D004279:DNA, Viral; D004268:DNA-Binding Proteins; D015696:Gene Products, tat; D016328:NF-kappa B; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D051996:Transcription Factor RelA; D014157:Transcription Factors; D054322:tat Gene Products, Human Immunodeficiency Virus