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)-kappaB 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.