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.
Subject(s)
HIV-1/genetics , Nuclear Proteins , Base Sequence , Binding Sites , DNA, Viral/genetics , DNA-Binding Proteins/metabolism , DNA-Binding Proteins/physiology , Gene Expression Regulation, Viral , Gene Products, tat/physiology , HIV Long Terminal Repeat , HIV-1/classification , Humans , Molecular Sequence Data , NF-kappa B/physiology , NFATC Transcription Factors , Phylogeny , Promoter Regions, Genetic , Proviruses , Sequence Alignment , Sequence Homology, Nucleic Acid , Transcription Factor RelA , Transcription Factors/metabolism , Transcription Factors/physiology , Transcription, Genetic , tat Gene Products, Human Immunodeficiency VirusABSTRACT
Magnetic resonance (MR) imaging is useful in evaluating the wide spectrum of diseases that cause nasal masses. MR imaging is most helpful in (a) defining tumor margins and possible intracranial extension and (b) differentiating tumor (which has intermediate, heterogeneous signal intensity on T2-weighted images) from concurrent postobstructive sinusitis and other infectious or inflammatory masses (which have high, homogeneous signal intensity on T2-weighted images if the secretions are well hydrated). The analysis becomes more complicated in cases with desiccated and mixed composition secretions. MR imaging also allows characterization of very vascular tumors, which show flow voids or marked enhancement. Low signal intensity on T1-weighted images and marked low signal intensity on T2-weighted images are characteristic of fungal sinusitis, and fat within a nasal mass indicates a dermoid or epidermoid cyst. Idiopathic midline granuloma, Wegener granulomatosis, and "cocaine nose" manifest as predominantly destructive midline masses. Despite the advantages of MR imaging, computed tomography remains the preferred imaging modality for evaluating nasal masses that contain calcification or originate from bone or cartilage.
