Longitudinal analysis of nef/long terminal repeat-deleted HIV-1 in blood and cerebrospinal fluid of a long-term survivor who developed HIV-associated dementia.
We studied the evolution and compartmentalization of nef/long terminal repeat (nef/LTR)-deleted human immunodeficiency virus type 1 (HIV-1) from a long-term survivor who developed HIV-associated dementia (HIVD). Analysis of sequential blood-derived HIV-1 isolated before and during HIVD revealed a persistent R5X4 phenotype and a progressive loss of nef/LTR sequence; in contrast, HIV-1 present in cerebrospinal fluid during HIVD had an R5 phenotype, distinct nef/LTR sequence of unique deletions and additional nuclear factor- kappa B sites and specificity factor-1 sites, and enhanced transcriptional activity, compared with the blood-derived isolates. Thus, nef/LTR-deleted HIV-1 strains may undergo compartmentalized evolution in long-term survivors and cause neurologic disease.
Churchill
Melissa
M
Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, Australia.
Sterjovski
Jasminka
J
Gray
Lachlan
L
Cowley
Daniel
D
Chatfield
Catherine
C
Learmont
Jennifer
J
Sullivan
John S
JS
Crowe
Suzanne M
SM
Mills
John
J
Brew
Bruce J
BJ
Wesselingh
Steven L
SL
McPhee
Dale A
DA
Gorry
Paul R
PR
D015526:AIDS Dementia Complex / Q000821:virology*; D000595:Amino Acid Sequence; D019143:Evolution, Molecular; D017353:Gene Deletion; D015686:Gene Products, env / Q000737:chemistry / Q000235:genetics; D015693:Gene Products, nef / Q000737:chemistry / Q000235:genetics*; D015752:Genes, env / Q000235:genetics; D015754:Genes, nef / Q000235:genetics; D015658:HIV Infections / Q000821:virology*; D016325:HIV Long Terminal Repeat / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D008137:Longitudinal Studies; D008969:Molecular Sequence Data; D010641:Phenotype; D054311:nef Gene Products, Human Immunodeficiency Virus
D015686:Gene Products, env; D015693:Gene Products, nef; D054311:nef Gene Products, Human Immunodeficiency Virus