Journal article
Development of co-selected single nucleotide polymorphisms in the viral promoter precedes the onset of human immunodeficiency virus type 1-associated neurocognitive impairment
Journal of neurovirology, v 17(1), pp 92-109
Feb 2011
PMID: 21225391
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The long terminal repeat (LTR) regulates gene expression of HIV-1 by interacting with multiple host and viral factors. Cross-sectional studies in the pre-HAART era demonstrated that single nucleotide polymorphisms (SNPs) in peripheral blood-derived LTRs (a C-to-T change at position 3 of C/EBP site I (3T) and at position 5 of Sp site III (5T)) increased in frequency as disease severity increased. Additionally, the 3T variant correlated with HIV-1-associated dementia. LTR sequences derived by longitudinal sampling of peripheral blood from a single patient in the DrexelMed HIV/AIDS Genetic Analysis Cohort resulted in the detection of the 3T and 5T co-selected SNPs before the onset of neurologic impairment, demonstrating that these SNPs may be useful in predicting HIV-associated neurological complications. The relative fitness of the LTRs containing the 3T and/or 5T co-selected SNPs as they evolve in their native patient-derived LTR backbone structure demonstrated a spectrum of basal and Tat-mediated transcriptional activities using the IIIB-derived Tat and colinear Tat derived from the same molecular clone containing the 3T/5T LTR SNP. In silico predictions utilizing colinear envelope sequence suggested that the patient’s virus evolved from an X4 to an R5 swarm prior to the development of neurological complications and more advanced HIV disease. These results suggest that the HIV-1 genomic swarm may evolve during the course of disease in response to selective pressures that lead to changes in prevalence of specific polymorphisms in the LTR,
env
, and/or
tat
that could predict the onset of neurological disease and result in alterations in viral function.
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Details
- Title
- Development of co-selected single nucleotide polymorphisms in the viral promoter precedes the onset of human immunodeficiency virus type 1-associated neurocognitive impairment
- Creators
- Luna Li - Department of Microbiology and Immunology, Drexel University College of Medicine, 245 N. 15th Street, MS #1013A, Philadelphia, PA 19102, USA. Center for Molecular Virology and Translational Neuroscience, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA, USABenjamas Aiamkitsumrit - Department of Microbiology and Immunology, Drexel University College of Medicine, 245 N. 15th Street, MS #1013A, Philadelphia, PA 19102, USA. Center for Molecular Virology and Translational Neuroscience, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA, USAVanessa Pirrone - Department of Microbiology and Immunology, Drexel University College of Medicine, 245 N. 15th Street, MS #1013A, Philadelphia, PA 19102, USA. Center for Molecular Virology and Translational Neuroscience, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA, USAMichael R Nonnemacher - Department of Microbiology and Immunology, Drexel University College of Medicine, 245 N. 15th Street, MS #1013A, Philadelphia, PA 19102, USA. Center for Molecular Virology and Translational Neuroscience, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA, USAAdam Wojno - Department of Microbiology and Immunology, Drexel University College of Medicine, 245 N. 15th Street, MS #1013A, Philadelphia, PA 19102, USA. Center for Molecular Virology and Translational Neuroscience, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA, USAShendra Passic - Department of Microbiology and Immunology, Drexel University College of Medicine, 245 N. 15th Street, MS #1013A, Philadelphia, PA 19102, USA. Center for Molecular Virology and Translational Neuroscience, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA, USAKatherine Flaig - Department of Microbiology and Immunology, Drexel University College of Medicine, 245 N. 15th Street, MS #1013A, Philadelphia, PA 19102, USA. Center for Molecular Virology and Translational Neuroscience, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA, USAEvelyn Kilareski - Department of Microbiology and Immunology, Drexel University College of Medicine, 245 N. 15th Street, MS #1013A, Philadelphia, PA 19102, USA. Center for Molecular Virology and Translational Neuroscience, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA, USABrandon Blakey - Department of Microbiology and Immunology, Drexel University College of Medicine, 245 N. 15th Street, MS #1013A, Philadelphia, PA 19102, USA. Center for Molecular Virology and Translational Neuroscience, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA, USAJade Ku - Department of Microbiology and Immunology, Drexel University College of Medicine, 245 N. 15th Street, MS #1013A, Philadelphia, PA 19102, USA. Center for Molecular Virology and Translational Neuroscience, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA, USANirzari Parikh - Department of Microbiology and Immunology, Drexel University College of Medicine, 245 N. 15th Street, MS #1013A, Philadelphia, PA 19102, USA. Center for Molecular Virology and Translational Neuroscience, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA, USARushabh Shah - Department of Microbiology and Immunology, Drexel University College of Medicine, 245 N. 15th Street, MS #1013A, Philadelphia, PA 19102, USA. Center for Molecular Virology and Translational Neuroscience, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA, USAJulio Martin-Garcia - Department of Microbiology and Immunology, Drexel University College of Medicine, 245 N. 15th Street, MS #1013A, Philadelphia, PA 19102, USA. Center for Molecular Virology and Translational Neuroscience, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA, USABrian Moldover - B-Tech Consulting, Ltd., Philadelphia, PA, USALaila Servance - Division of Infectious Disease and HIV Medicine, Department of Medicine, Drexel University College of Medicine, Philadelphia, PA, USADavid Downie - Division of Infectious Disease and HIV Medicine, Department of Medicine, Drexel University College of Medicine, Philadelphia, PA, USASharon Lewis - Division of Infectious Disease and HIV Medicine, Department of Medicine, Drexel University College of Medicine, Philadelphia, PA, USAJeffrey M Jacobson - Department of Microbiology and Immunology, Drexel University College of Medicine, 245 N. 15th Street, MS #1013A, Philadelphia, PA 19102, USA. Center for Molecular Virology and Translational Neuroscience, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA, USA. Center for Clinical and Translational Medicine, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA, USA. Division of Infectious Disease and HIV Medicine, Department of Medicine, Drexel University College of Medicine, Philadelphia, PA, USADennis Kolson - Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA, USABrian Wigdahl - Department of Microbiology and Immunology, Drexel University College of Medicine, 245 N. 15th Street, MS #1013A, Philadelphia, PA 19102, USA. Center for Molecular Virology and Translational Neuroscience, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA, USA. Center for Clinical and Translational Medicine, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA, USA
- Publication Details
- Journal of neurovirology, v 17(1), pp 92-109
- Publisher
- Springer Nature
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:000289580200011
- Scopus ID
- 2-s2.0-79952941684
- Other Identifier
- 991014877892404721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Neurosciences
- Virology