title: 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.
abstract: 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.
authors.affiliation: Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, Australia.
authors.forename: Melissa
authors.initials: M
authors.lastname: Churchill
authors.forename: Jasminka
authors.initials: J
authors.lastname: Sterjovski
authors.forename: Lachlan
authors.initials: L
authors.lastname: Gray
authors.forename: Daniel
authors.initials: D
authors.lastname: Cowley
authors.forename: Catherine
authors.initials: C
authors.lastname: Chatfield
authors.forename: Jennifer
authors.initials: J
authors.lastname: Learmont
authors.forename: John S
authors.initials: JS
authors.lastname: Sullivan
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Crowe
authors.forename: John
authors.initials: J
authors.lastname: Mills
authors.forename: Bruce J
authors.initials: BJ
authors.lastname: Brew
authors.forename: Steven L
authors.initials: SL
authors.lastname: Wesselingh
authors.forename: Dale A
authors.initials: DA
authors.lastname: McPhee
authors.forename: Paul R
authors.initials: PR
authors.lastname: Gorry
mesh_terms: 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
chemical_list: D015686:Gene Products, env; D015693:Gene Products, nef; D054311:nef Gene Products, Human Immunodeficiency Virus