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.
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.
Churchill
Melissa J
MJ
The Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, Victoria, Australia.
Figueiredo
Anna
A
Cowley
Daniel
D
Gray
Lachlan
L
Purcell
Damian Fj
DF
Sullivan
John S
JS
McPhee
Dale A
DA
Wesselingh
Steven L
SL
Brew
Bruce J
BJ
Gorry
Paul R
PR
D015526:AIDS Dementia Complex / Q000821:virology*; D017353:Gene Deletion; D015967:Gene Expression Regulation, Viral; D015693:Gene Products, nef / Q000097:blood / Q000134:cerebrospinal fluid / Q000235:genetics*; D015696:Gene Products, tat / Q000235:genetics; D016325:HIV Long Terminal Repeat / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics* / Q000472:pathogenicity; D006801:Humans; D015533:Transcriptional Activation; D019562:Viral Load; D014774:Virulence; D054311:nef Gene Products, Human Immunodeficiency Virus; D054322:tat Gene Products, Human Immunodeficiency Virus
D015693:Gene Products, nef; D015696:Gene Products, tat; D054311:nef Gene Products, Human Immunodeficiency Virus; D054322:tat Gene Products, Human Immunodeficiency Virus