title: Genetic features of cerebrospinal fluid-derived subtype B HIV-1 tat.
abstract: Since HIV-1 Tat has been associated with neurocognitive dysfunction, we investigated 60 HIV-1 subtype B-infected individuals who were characterized for neurocognitive functioning and had paired CSF and blood plasma samples available. To avoid issues with repeated sampling, we generated population-based HIV-1 tat sequences from each compartment and evaluated these data using a battery of phylogenetic, statistical, and machine learning tools. These analyses identified position HXB2 5905 within the cysteine-rich domain of tat as a signature of CSF-derived HIV-1, and a higher number of mixed bases in CSF, as measure of diversity, was associated with HIV-associated neurocognitive disorder. Since identified mutations were synonymous, we evaluated the predicted secondary RNA structures, which showed that this mutation altered secondary structure. As a measure of divergence, the genetic distance between the blood and CSF-derived tat was inversely correlated with current and nadir CD4+ T cell counts. These data suggest that specific HIV-1 features of tat influence neurotropism and neurocognitive impairment.
authors.affiliation: Department of Internal Medicine and AIDS Research Institute, Yonsei University College of Medicine, 250 Seongsanno, Seodaemun-gu, Seoul 120-752, South Korea. seran@yuhs.ac
authors.forename: Jun Yong
authors.initials: JY
authors.lastname: Choi
authors.forename: George K
authors.initials: GK
authors.lastname: Hightower
authors.forename: Joseph K
authors.initials: JK
authors.lastname: Wong
authors.forename: Robert
authors.initials: R
authors.lastname: Heaton
authors.forename: Steven
authors.initials: S
authors.lastname: Woods
authors.forename: Igor
authors.initials: I
authors.lastname: Grant
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Marcotte
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Ellis
authors.forename: Scott L
authors.initials: SL
authors.lastname: Letendre
authors.forename: Ann C
authors.initials: AC
authors.lastname: Collier
authors.forename: Christina M
authors.initials: CM
authors.lastname: Marra
authors.forename: David B
authors.initials: DB
authors.lastname: Clifford
authors.forename: Benjamin B
authors.initials: BB
authors.lastname: Gelman
authors.forename: Justin C
authors.initials: JC
authors.lastname: McArthur
authors.forename: Susan
authors.initials: S
authors.lastname: Morgello
authors.forename: David M
authors.initials: DM
authors.lastname: Simpson
authors.forename: J Allen
authors.initials: JA
authors.lastname: McCutchan
authors.forename: Douglas D
authors.initials: DD
authors.lastname: Richman
authors.forename: Davey M
authors.initials: DM
authors.lastname: Smith
mesh_terms: D015526:AIDS Dementia Complex / Q000097:blood / Q000134:cerebrospinal fluid / Q000821:virology*; D000328:Adult; D001185:Artificial Intelligence; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology; D005260:Female; D018740:Genetic Heterogeneity; D015497:HIV-1 / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009690:Nucleic Acid Conformation; D017434:Protein Structure, Tertiary; D012367:RNA, Viral / Q000097:blood / Q000134:cerebrospinal fluid / Q000235:genetics*; D017422:Sequence Analysis, DNA; D056189:Viral Tropism; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000097:blood / Q000134:cerebrospinal fluid / Q000235:genetics*
chemical_list: D012367:RNA, Viral; D054322:tat Gene Products, Human Immunodeficiency Virus