Alterations in HIV-1 LTR promoter activity during AIDS progression
Department of Pediatrics; Program in Molecular Medicine
Medical Subject Headings
Adolescent; Adult; Base Sequence; Cell Line; Child; Child, Preschool; Disease Progression; HIV Infections; HIV Long Terminal Repeat; HIV-1; Humans; Jurkat Cells; Leukocytes, Mononuclear; Middle Aged; Molecular Sequence Data; *Mutation; Promoter Regions, Genetic; U937 Cells
Immunology and Infectious Disease | Pediatrics
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.
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Citation: Virology. 2003 Dec 5;317(1):109-18. doi:10.1016/j.virol.2003.08.034