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Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/12034
Title: Interactions between human immunodeficiency virus (HIV)-1 Vpr expression and innate immunity influence neurovirulence
Authors: Hong Na
Shaona Acharjee
Gareth Jones
Pornpun Vivithanaporn
Farshid Noorbakhsh
Nicola McFarlane
Ferdinand Maingat
Klaus Ballanyi
Carlos A. Pardo
Éric A. Cohen
Christopher Power
University of Alberta
University of Calgary
Mahidol University
The Johns Hopkins School of Medicine
Institut de Recherches Cliniques de Montreal
Keywords: Immunology and Microbiology;Medicine
Issue Date: 6-Jun-2011
Citation: Retrovirology. Vol.8, (2011)
Abstract: Background: Viral diversity and abundance are defining properties of human immunodeficiency virus (HIV)-1's biology and pathogenicity. Despite the increasing availability of antiretroviral therapy, HIV-associated dementia (HAD) continues to be a devastating consequence of HIV-1 infection of the brain although the underlying disease mechanisms remain uncertain. Herein, molecular diversity within the HIV-1 non-structural gene, Vpr, was examined in RNA sequences derived from brain and blood of HIV/AIDS patients with or without HIV-associated dementia (HAD) together with the ensuing pathobiological effects.Results: Cloned brain- and blood-derived full length vpr alleles revealed that amino acid residue 77 within the brain-derived alleles distinguished HAD (77Q) from non-demented (ND) HIV/AIDS patients (77R) (p < 0.05) although vpr transcripts were more frequently detected in HAD brains (p < 0.05). Full length HIV-1 clones encoding the 77R-ND residue induced higher IFN-α, MX1 and BST-2 transcript levels in human glia relative to the 77Q-HAD encoding virus (p < 0.05) but both viruses exhibited similar levels of gene expression and replication. Myeloid cells transfected with 77Q-(pVpr77Q-HAD), 77R (pVpr77R-ND) or Vpr null (pVpr (-) )-containing vectors showed that the pVpr77R-ND vector induced higher levels of immune gene expression (p < 0.05) and increased neurotoxicity (p < 0.05). Vpr peptides (amino acids 70-96) containing the 77Q-HAD or 77R-ND motifs induced similar levels of cytosolic calcium activation when exposed to human neurons. Human glia exposed to the 77R-ND peptide activated higher transcript levels of IFN-α, MX1, PRKRA and BST-2 relative to 77Q-HAD peptide (p < 0.05). The Vpr 77R-ND peptide was also more neurotoxic in a concentration-dependent manner when exposed to human neurons (p < 0.05). Stereotaxic implantation of full length Vpr, 77Q-HAD or 77R-ND peptides into the basal ganglia of mice revealed that full length Vpr and the 77R-ND peptide caused greater neurobehavioral deficits and neuronal injury compared with 77Q-HAD peptide-implanted animals (p < 0.05).Conclusions: These observations underscored the potent neuropathogenic properties of Vpr but also indicated viral diversity modulates innate neuroimmunity and neurodegeneration. © 2011 Na et al; licensee BioMed Central Ltd.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=79957904923&origin=inward
http://repository.li.mahidol.ac.th/dspace/handle/123456789/12034
ISSN: 17424690
Appears in Collections:Scopus 2011-2015

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