Journal article
Sequence variation within the HIV-1 LTR correlates with brain regionalization and HIV-1-associated dementia
Journal of neurovirology, Vol.13, pp.115-115
01 Jan 2007
Abstract
The long terminal repeat (LTR) regulates human immunodeficiency type 1 (HIV-1) viral gene expression during the course of infection. The activity of the LTR is regulated by the relative availability of viral and cellular transcriptional control proteins and the genetic variation that accumulates during replication. The C/EBP site II consensus B (conB) variant has been shown to be highly conserved in brain-derived HIV-1 LTR populations, and that LTRs containing C/EBP site II 4C and 6G variants were only found in brain tissue of patients with HIV-1-associated dementia (HIVD). A statistically significant difference was also found in the regional distribution of LTRs containing the C/EBP site II conB, 4C, or 6G variant in brain regions derived from patients with and without HIVD. A low affinity C/EBP site II 4C variant accumulates in the cerebellum, a region exhibiting little viral gene expression, while the high affinity C/EBP site II 6G variant accumulated in the mid-frontal gyrus, a site of highly productive replication. A 3T C/EBP site I variant was identified in 25% of brain-derived LTRs from patients diagnosed with HIVD, but was absent in patients without dementia. LTRs containing a C/EBP site I 6G variant were found to accumulate in a highly specific manner in the head of caudate and the C/EBP site I 3T variant accumulated in the mid-frontal gyrus. In conclusion, distinct LTR populations with specific C/EBP site I and II configurations were found in different neuroanatomical regions of the brain and correlated with neurological disease.
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Details
- Title
- Sequence variation within the HIV-1 LTR correlates with brain regionalization and HIV-1-associated dementia
- Creators
- J PitcherM NonnemacherA AlexakiE KilareskiS GartnerB Wigdahl
- Publication Details
- Journal of neurovirology, Vol.13, pp.115-115
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Identifiers
- 991019170482204721