Journal of NeuroVirology

, Volume 13, Issue 2, pp 173–184

Brain-derived human immunodeficiency virus-1 Tat exerts differential effects on LTR transactivation and neuroimmune activation

Authors

  • Leonie A. Boven
    • Department of ImmunologyErasmus Medical Center
    • Department of Clinical NeurosciencesUniversity of Calgary
  • Farshid Noorbakhsh
    • Department of ImmunologyTehran University of Medical Sciences
  • Gerben Bouma
    • Eijkman-Winkler Institute, Section of NeuroimmunologyUniversity Medical Center
  • Ruurd van der Zee
    • Department of Infectious Diseases and ImmunologyFaculty of Veterinary Medicine, Utrecht University
  • Diana L. Vargas
    • Department of NeurologyJohns Hopkins University
  • Carlos Pardo
    • Department of NeurologyJohns Hopkins University
  • Justin C. McArthur
    • Department of NeurologyJohns Hopkins University
  • Hans S. L. M. Nottet
    • Eijkman-Winkler Institute, Section of NeuroimmunologyUniversity Medical Center
    • Department of Clinical NeurosciencesUniversity of Calgary
    • Department of MedicineUniversity of Alberta Heritage Medical Research Centre
Article

DOI: 10.1080/13550280701258399

Cite this article as:
Boven, L.A., Noorbakhsh, F., Bouma, G. et al. Journal of NeuroVirology (2007) 13: 173. doi:10.1080/13550280701258399

Abstract

Molecular diversity within brain-derived HIV-1 sequences is highly variable depending on the individual gene examined and the neurological status of the patient. Herein, we examined different brain-derived human immunodeficiency virus (HIV)-1 tat sequences in terms of their effects on LTR transactivation and host gene induction in neural cells. Astrocytic and monocytoid cells co-transfected with prototypic tat clones derived from non-demented (ND) (n = 3) and demented (HAD) (n = 3) AIDS patients and different HIV-LTR constructs revealed that LTR transactivation mediated by tat clones derived from HAD patients was decreased (p < 0.05). A Tat-derived peptide containing the amino acid 24–38 domain from a ND clone caused down-regulation of the LTR transactivation (p < 0.05) in contrast to peptides from other Tat regions derived from HAD and ND tat clones. Both brain-derived HAD and ND tat constructs were able to induce the host immune genes, MCP-1 and IL-1β. Microarray analysis revealed several host genes were selectively upregulated by a HAD-derived tat clone including an enzyme mediating heparan sulphate synthesis, HS3ST3B1 (p < 0.05), which was also found to be increased in the brains of patients with HAD. Expression of the pro-apoptotic gene, PDCD7, was reduced in cells transfected with the HAD-derived tat clone and moreover, this gene was also suppressed in monocytoid cells infected with a neurotropic HIV-1 strain. Thus, mutations within the HIV-1 tat gene may exert pathogenic effects contributing to the development of HAD, which are independent of its effects on LTR transactivation.

Keywords

astrocytechemokinecytokineHIV-1LTRmacrophagemicroarrayTat

Copyright information

© Journal of NeuroVirology, Inc. 2007