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Author Dampier, Will ♦ Antell, Gregory C. ♦ Aiamkitsumrit, Benjamas ♦ Nonnemacher, Michael R. ♦ Jacobson, Jeffrey M. ♦ Pirrone, Vanessa ♦ Zhong, Wen ♦ Kercher, Katherine ♦ Passic, Shendra ♦ Williams, Jean W. ♦ James, Tony ♦ Devlin, Kathryn N. ♦ Giovannetti, Tania ♦ Libon, David J. ♦ Szep, Zsofia ♦ Ehrlich, Garth D. ♦ Wigdahl, Brian ♦ Krebs, Fred C.
Source SpringerLink
Content type Text
Publisher Springer International Publishing
File Format PDF
Copyright Year ©2016
Language English
Subject Domain (in DDC) Technology ♦ Medicine & health
Subject Keyword HIV ♦ Vpr ♦ HAND ♦ Neuropathogenesis ♦ GDS ♦ Quasispecies ♦ Sequence ♦ Neurosciences ♦ Virology ♦ Infectious Diseases ♦ Immunology ♦ Neurology
Abstract Even in the era of combination antiretroviral therapies used to combat human immunodeficiency virus type 1 (HIV-1) infection, up to 50 % of well-suppressed HIV-1-infected patients are still diagnosed with mild neurological deficits referred to as HIV-associated neurocognitive disorders (HAND). The multifactorial nature of HAND likely involves the HIV-1 accessory protein viral protein R (Vpr) as an agent of neuropathogenesis. To investigate the effect of naturally occurring variations in Vpr on HAND in well-suppressed HIV-1-infected patients, bioinformatic analyses were used to correlate peripheral blood-derived Vpr sequences with patient neurocognitive performance, as measured by comprehensive neuropsychological assessment and the resulting Global Deficit Score (GDS). Our studies revealed unique associations between GDS and the presence of specific amino acid changes in peripheral blood-derived Vpr sequences [neuropsychological impairment Vpr (niVpr) variants]. Amino acids N41 and A55 in the Vpr sequence were associated with more pronounced neurocognitive deficits (higher GDS). In contrast, amino acids I37 and S41 were connected to measurably lower GDS. All niVpr variants were also detected in DNA isolated from HIV-1-infected brain tissues. The implication of these results is that niVpr variants alter the genesis and/or progression of HAND through differences in Vpr-mediated effects in the peripheral blood and/or the brain.
ISSN 13550284
Age Range 18 to 22 years ♦ above 22 year
Educational Use Research
Education Level UG and PG
Learning Resource Type Article
Publisher Date 2016-07-11
Publisher Place Cham, Switzerland
e-ISSN 15382443
Journal Journal of NeuroVirology
Volume Number 23
Issue Number 1
Page Count 12
Starting Page 113
Ending Page 124


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Source: SpringerLink