Journal article
Impact of low affinity C/EBP and Sp binding sites on HIV-1 replication and relevance to commonly encountered LTR genetic variants observed early and late in HIV disease
Journal of neurovirology, Vol.13, pp.92-92
01 Jan 2007
Abstract
Recent studies have identified two genetic variants in the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) in the peripheral blood of infected patients that correlate with early and late HIV disease. One incorporates a C-to-T change in C/EBP binding site I (3T), and the other incorporates a C-to-T change at position 5 of Sp site III (5T). Interestingly, in peripheral blood-derived LTRs, 94% of patients who had the 3T variant also had the 5T variant within the same LTR. In LTRs isolated from the brains of HIV-infected patients, 3T C/EBP site I and 5T Sp site III were only found in patients who had HIV-associated dementia (HIVD), but were not found in patients without HIVD. The overall goal of these studies is to determine the effect of these particular genetic variants on viral replication. The 3T, 5T, and 3T5T double variant were incorporated into the HIV-1 LAI infectious molecular clone, and infectious viral particles were generated by transfection of the molecular clone into 293T cells. The results of infection of monocytic U-937 and lymphocytic Jurkat cell lines, as well as primary peripheral blood mononuclear cells and monocyte-derived macrophages with genetically altered viruses carrying the 3T, 5T, and 3T/5T C/EBP and/or Sp transcription factor binding site variants has suggested that the single and double base pair changes in the viral LTR have impact of viral replication capability. In addition, the effect of cytokine stimulation of these HIV-1 infected cell populations has also been examined.
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Details
- Title
- Impact of low affinity C/EBP and Sp binding sites on HIV-1 replication and relevance to commonly encountered LTR genetic variants observed early and late in HIV disease
- Creators
- E KilareskiV PirroneS PassicM NonnemacherB Wigdahl
- Publication Details
- Journal of neurovirology, Vol.13, pp.92-92
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Identifiers
- 991019170441504721