Specific amino acids in HIV-1 Vpr are significantly associated with differences in patient neurocognitive status View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-07-11

AUTHORS

Will Dampier, Gregory C. Antell, Benjamas Aiamkitsumrit, Michael R. Nonnemacher, Jeffrey M. Jacobson, Vanessa Pirrone, Wen Zhong, Katherine Kercher, Shendra Passic, Jean W. Williams, Tony James, Kathryn N. Devlin, Tania Giovannetti, David J. Libon, Zsofia Szep, Garth D. Ehrlich, Brian Wigdahl, Fred C. Krebs

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. More... »

PAGES

113-124

References to SciGraph publications

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  • Journal

    TITLE

    Journal of NeuroVirology

    ISSUE

    1

    VOLUME

    23

    Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1007/s13365-016-0462-3

    DOI

    http://dx.doi.org/10.1007/s13365-016-0462-3

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1024717003

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/27400931


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