title: Alterations in HIV-1 LTR promoter activity during AIDS progression.
abstract: HIV-1 variants evolving in AIDS patients frequently show increased replicative capacity compared to those present during early asymptomatic infection. It is known that late stage HIV-1 variants often show an expanded coreceptor tropism and altered Nef function. In the present study we investigated whether enhanced HIV-1 LTR promoter activity might also evolve during disease progression. Our results demonstrate increased LTR promoter activity after AIDS progression in 3 of 12 HIV-1-infected individuals studied. Further analysis revealed that multiple alterations in the U3 core-enhancer and in the transactivation-response (TAR) region seem to be responsible for the enhanced functional activity. Our findings show that in a subset of HIV-1-infected individuals enhanced LTR transcription contributes to the increased replicative potential of late stage virus isolates and might accelerate disease progression.
authors.affiliation: Institute for Clinical and Molecular Virology, University of Erlangen-Nürnberg, Schlossgarten 4, 91054 Erlangen, Germany.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Hiebenthal-Millow
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Greenough
authors.forename: Doreen B
authors.initials: DB
authors.lastname: Bretttler
authors.forename: Michael
authors.initials: M
authors.lastname: Schindler
authors.forename: Steffen
authors.initials: S
authors.lastname: Wildum
authors.forename: John L
authors.initials: JL
authors.lastname: Sullivan
authors.forename: Frank
authors.initials: F
authors.lastname: Kirchhoff
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D002460:Cell Line; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D015658:HIV Infections / Q000503:physiopathology* / Q000821:virology; D016325:HIV Long Terminal Repeat / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics / Q000472:pathogenicity*; D006801:Humans; D019169:Jurkat Cells; D007963:Leukocytes, Mononuclear / Q000821:virology; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D011401:Promoter Regions, Genetic / Q000235:genetics*; D020298:U937 Cells