Transcriptional activity of blood-and cerebrospinal fluid–derived nef/long-terminal repeat sequences isolated from a slow progressor infected with nef-deleted human immunodeficiency virus type 1 (HIV-1) who developed HIV-associated dementia

Abstract

The authors studied the transcriptional activity of blood-and cerebrospinal fluid (CSF)-derived nef/long-terminal repeat (LTR) sequences isolated from a slow progressor infected with nef-deleted human immunodeficiency virus type 1 (HIV-1) who developed HIV-associated dementia (HIVD). The transcriptional activity of CSF-derived nef/LTR clones isolated during HIVD was up to 4.5-fold higher than blood-derived clones isolated before and during HIVD when tested under basal, phorbol 12-myristate 13-acetate-(PMA-), and Tat-activated conditions, and was associated with the presence of duplicated nuclear factor (NF)-κB and specificity factor-1 (Sp-1) binding sites coupled with a truncated nef sequence, increased replication capacity, and high CSF viral load. Thus, nef and LTR mutations that augment transcription may contribute to neuropathogenesis of nef-deleted HIV-1. Journal of NeuroVirology (2006) 12, 219–228.

Keywords:

• HIV-1
• Nef
• NF-κB
• neurotropism
• Sp-1

This study was supported by grants from the Australian National Health and Medical Research Council (NHMRC) to S.L.W. (358399) and P.R.G. (251520), grants from the Australian National Center for HIV Virology Research to M.J.C. and D.M., and a grant from NIH/NIAID to P.R.G. (R21-AI054207). P.R.G. is a recipient of an NHMRC R. Douglas Wright Biomedical Career Development Award.