Journal article
HIV-1 LTR C/EBP binding site sequence configurations preferentially encountered in brain lead to enhanced C/EBP factor binding and increased LTR-specific activity
Journal of neurovirology, v 7(3)
May 2001
PMID: 11517398
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Recent studies have shown that two CAAT/enhancer binding protein (C/EBP) sites are critically important for efficient human immunodeficiency virus (HIV) type 1 (HIV-l) replication within cells of the monocyte/macrophage lineage, a primary cell type infected by HIV-1 and a potentially important vehicle for transport of virus to the central nervous system (CNS). Given the relevance of HIV-1 LTR sequence variation with respect to HIV-1 replication within monocyte populations and the important role that monocyte tropism likely plays in HIV-1 infection of the brain, C/EBP site sequence variation was examined within peripheral blood- and brain-derived LTR populations. Brain-derived LTRs commonly possessed a C/EBP site I configuration (6G, comprised of a thymidine to guanosine substitution with respect to the clade B consensus sequence at position 6 of C/EBP site I) that leads to enhanced binding of C/EBP proteins over that observed with the HIV-1 clade B consensus sequence at this site. In contrast, the 6G C/EBP site I configuration appeared infrequently within sequenced peripheral blood-derived LTRs. In addition, C/EBP site II was even more highly conserved in brain-derived HIV-1 LTR populations than site I. This was not the case with peripheral blood-derived LTR C/EBP site II sequences. The high degree of C/EBP site II conservation in brain-derived LTRs was likely important in LTR regulation since the clade B consensus sequence conserved at C/EBP site II recruited high amounts of C/EBP family members. Transient transfection analyses indicated that conservation of the strong C/EBP site II in brain-derived LTRs was likely due to important interactions with Tat. Overall, brain-derived HIV-1 LTRs preferentially contained two highly reactive C/EBP binding sites, which may suggest that these sites play important roles in LTR-directed transcription during invasion and maintenance of HIV-1 in the central nervous system.
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Details
- Title
- HIV-1 LTR C/EBP binding site sequence configurations preferentially encountered in brain lead to enhanced C/EBP factor binding and increased LTR-specific activity
- Creators
- Heather Ross - Department of Microbiology and Immunology (H107) The Pennsylvania State University College of Medicine 500 University Drive P. O. Box 850 17033 Hershey PA USASuzanne Gartner - Department of Neurology The Johns Hopkins School of Medicine Baltimore Maryland USAJustin McArthur - Department of Neurology The Johns Hopkins School of Medicine Baltimore Maryland USAJohn Corboy - Department of Neurology The University of Colorado, Health Sciences Center Denver Colorado USAJohn McAllister - Department of Microbiology and Immunology (H107) The Pennsylvania State University College of Medicine 500 University Drive P. O. Box 850 17033 Hershey PA USAScott Millhouse - Department of Microbiology and Immunology (H107) The Pennsylvania State University College of Medicine 500 University Drive P. O. Box 850 17033 Hershey PA USABrian Wigdahl - Department of Microbiology and Immunology (H107) The Pennsylvania State University College of Medicine 500 University Drive P. O. Box 850 17033 Hershey PA USA
- Publication Details
- Journal of neurovirology, v 7(3)
- Publisher
- Springer-Verlag; New York
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:000169987700006
- Scopus ID
- 2-s2.0-0034922779
- Other Identifier
- 991014877972904721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Neurosciences
- Virology