Genetic variants within the HIV-1 LTR may be predictive of HAD

B Irish; M Nonnemacher; B Wigdahl

Human immunodeficiency virus type 1 (HIV-1) proviral DNA with specific binding site sequence variants within the long terminal repeat (LTR), which arise during the course of infection may have functional implications relative to LTR activation, viral replication, as well predictive value relative to progressive neurological disease. The LTR regulates HIV-1 viral gene expression via its interaction with multiple viral and host factors, including members of the CCAAT/enhancer binding protein (C/EBP) and Sp transcription factor families. We have examined sequence variation at C/EBP sites I and II, and Sp sites I, II, and III in peripheral blood (PB)-derived LTRs from HIV-1-infected patients representing increasing degrees of disease severity. The 3T configuration of C/EBP site I (C-to-T change at nucleotide position 3) and 5T configuration of Sp site III (C-to-T change at nucleotide position 5) were the only variants examined that were found in low frequencies in PB-derived LTRs derived from patients at early stages of HIV-1 disease, and at relatively high frequencies in patients in late stage disease. Sequence variation at these sites was also examined in LTRs derived from various brain compartments of patients both with and without HAD (the 3T C/EBP site I variant was identified in 25% of brain-derived LTRs from patients diagnosed with HAD, but was absent in patients not suffering from dementia). These results suggest that 3T C/EBP site I, and possibly 5T Sp site III may prove valuable in assessing the likelihood of HIV-1-infected individuals developing HAD.

Genetic variants within the HIV-1 LTR may be predictive of HAD

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Genetic variants within the HIV-1 LTR may be predictive of HAD

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Abstract

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