Journal of NeuroVirology

, Volume 7, Issue 3, pp 235–249

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

Authors

  • Heather L. Ross
    • Department of Microbiology and Immunology (H107)The Pennsylvania State University College of Medicine
  • Suzanne Gartner
    • Department of NeurologyThe Johns Hopkins School of Medicine
  • Justin C. McArthur
    • Department of NeurologyThe Johns Hopkins School of Medicine
  • John R. Corboy
    • Department of NeurologyThe University of Colorado, Health Sciences Center
  • John J. McAllister
    • Department of Microbiology and Immunology (H107)The Pennsylvania State University College of Medicine
  • Scott Millhouse
    • Department of Microbiology and Immunology (H107)The Pennsylvania State University College of Medicine
    • Department of Microbiology and Immunology (H107)The Pennsylvania State University College of Medicine
Article

DOI: 10.1080/13550280152403281

Cite this article as:
Ross, H.L., Gartner, S., McArthur, J.C. et al. Journal of NeuroVirology (2001) 7: 235. doi:10.1080/13550280152403281

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.

Copyright information

© Journal of NeuroVirology, Inc. 2001