HIV-1 LTR C/EBP binding site sequence configurations preferenstially encountered in brain lead to enhanced C/EBP factor binding and increased LTR-specific activity

H. L. Ross, S. Gartner, J. C. McArthur, J. R. Corboy, J. J. McAllister, S. Millhouse, B. Wigdahl

Research output: Contribution to journalArticle

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-1) 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.

Original languageEnglish (US)
Pages (from-to)235-249
Number of pages15
JournalJournal of neurovirology
Volume7
Issue number3
DOIs
StatePublished - Aug 8 2001
Externally publishedYes

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Virology

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