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

J Neurovirol. 2017 Apr;23(2):319-328. doi: 10.1007/s13365-016-0503-y. Epub 2016 Dec 2.

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: C30C31 dicysteine motif; Clade C; HIV; Neuroimaging; Tat C31S.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Amino Acid Substitution*
  • Brain Mapping
  • Case-Control Studies
  • Caudate Nucleus / diagnostic imaging
  • Caudate Nucleus / pathology
  • Caudate Nucleus / virology
  • Corpus Callosum / diagnostic imaging
  • Corpus Callosum / pathology
  • Corpus Callosum / virology
  • Diffusion Tensor Imaging / instrumentation
  • Diffusion Tensor Imaging / methods*
  • Female
  • Gene Expression
  • Genetic Variation
  • Genotype
  • Gray Matter / diagnostic imaging
  • Gray Matter / pathology
  • Gray Matter / virology
  • HIV / genetics*
  • HIV / pathogenicity
  • HIV Infections / diagnostic imaging*
  • HIV Infections / pathology
  • HIV Infections / virology
  • Humans
  • Image Processing, Computer-Assisted
  • Male
  • Putamen / diagnostic imaging
  • Putamen / pathology
  • Putamen / virology
  • Thalamus / diagnostic imaging
  • Thalamus / pathology
  • Thalamus / virology
  • White Matter / diagnostic imaging
  • White Matter / pathology
  • White Matter / virology
  • tat Gene Products, Human Immunodeficiency Virus / genetics*

Substances

  • tat Gene Products, Human Immunodeficiency Virus