Journal of NeuroVirology

, Volume 23, Issue 2, pp 319–328

Neuroimaging abnormalities in clade C HIV are independent of Tat genetic diversity

  • Robert H. Paul
  • Sarah Phillips
  • Jacqueline Hoare
  • David H. Laidlaw
  • Ryan Cabeen
  • Gayla R. Olbricht
  • Yuqing Su
  • Dan J. Stein
  • Susan Engelbrecht
  • Soraya Seedat
  • Lauren E. Salminen
  • Laurie M. Baker
  • Jodi Heaps
  • John Joska
Article

DOI: 10.1007/s13365-016-0503-y

Cite this article as:
Paul, R.H., Phillips, S., Hoare, J. et al. J. Neurovirol. (2017) 23: 319. doi:10.1007/s13365-016-0503-y

Abstract

Controversy remains regarding the neurotoxicity of clade C human immunodeficiency virus (HIV-C). When examined in preclinical studies, a cysteine to serine substitution in the C31 dicysteine motif of the HIV-C Tat protein (C31S) results in less severe brain injury compared to other viral clades. By contrast, patient cohort studies identify significant neuropsychological impairment among HIV-C individuals independent of Tat variability. The present study clarified this discrepancy by examining neuroimaging markers of brain integrity among HIV-C individuals with and without the Tat substitution. Thirty-seven HIV-C individuals with the Tat C31S substitution, 109 HIV-C individuals without the Tat substitution (C31C), and 34 HIV− controls underwent 3T structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). Volumes were determined for the caudate, putamen, thalamus, corpus callosum, total gray matter, and total white matter. DTI metrics included fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD). Tracts of interest included the anterior thalamic radiation (ATR), cingulum bundle (CING), uncinate fasciculus (UNC), and corpus callosum (CC). HIV+ individuals exhibited smaller volumes in subcortical gray matter, total gray matter and total white matter compared to HIV− controls. HIV+ individuals also exhibited DTI abnormalities across multiple tracts compared to HIV− controls. By contrast, neither volumetric nor diffusion indices differed significantly between the Tat C31S and C31C groups. Tat C31S status is not a sufficient biomarker of HIV-related brain integrity in patient populations. Clinical attention directed at brain health is warranted for all HIV+ individuals, independent of Tat C31S or clade C status.

Keywords

HIV Clade C C30C31 dicysteine motif Tat C31S Neuroimaging 

Funding information

Funder NameGrant NumberFunding Note
National Institute of Mental Health
  • R01083578

Copyright information

© Journal of NeuroVirology, Inc. 2016

Authors and Affiliations

  • Robert H. Paul
    • 1
  • Sarah Phillips
    • 1
  • Jacqueline Hoare
    • 2
  • David H. Laidlaw
    • 3
  • Ryan Cabeen
    • 3
  • Gayla R. Olbricht
    • 4
  • Yuqing Su
    • 4
  • Dan J. Stein
    • 2
  • Susan Engelbrecht
    • 5
  • Soraya Seedat
    • 6
  • Lauren E. Salminen
    • 7
  • Laurie M. Baker
    • 1
  • Jodi Heaps
    • 1
  • John Joska
    • 2
  1. 1.Missouri Institute of Mental HealthUniversity of MissouriSt. LouisUSA
  2. 2.Department of Psychiatry and Mental HealthUniversity of Cape TownCape TownSouth Africa
  3. 3.Department of Computer ScienceBrown UniversityProvidenceUSA
  4. 4.Department of Mathematics and StatisticsMissouri University of Science and TechnologyRollaUSA
  5. 5.Division of Medical VirologyStellenbosch University and National Health Laboratory Services (NHLS)Cape TownSouth Africa
  6. 6.MRC Unit on Anxiety and Stress Disorders, Department of PsychiatryUniversity of StellenboschStellenboschSouth Africa
  7. 7.Mark and Mary Stevens Neuroimaging and Informatics InstituteUniversity of Southern CaliforniaLos AngelesUSA

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