Journal of NeuroVirology

, Volume 24, Issue 1, pp 1–15 | Cite as

Brain-specific HIV Nef identified in multiple patients with neurological disease

  • Susanna L. LamersEmail author
  • Gary B. Fogel
  • Enoch S. Liu
  • Andrew E. Barbier
  • Christopher W. Rodriguez
  • Elyse J. Singer
  • David J. Nolan
  • Rebecca Rose
  • Michael S. McGrath


HIV-1 Nef is a flexible, multifunctional protein with several cellular targets that is required for pathogenicity of the virus. This protein maintains a high degree of genetic variation among intra- and inter-host isolates. HIV Nef is relevant to HIV-associated neurological diseases (HAND) in patients treated with combined antiretroviral therapy because of the protein’s role in promoting survival and migration of infected brain macrophages. In this study, we analyzed 2020 HIV Nef sequences derived from 22 different tissues and 31 subjects using a novel computational approach. This approach combines statistical regression and evolved neural networks (ENNs) to classify brain sequences based on the physical and chemical characteristics of functional Nef domains. Based on training, testing, and validation data, the method successfully classified brain Nef sequences at 84.5% and provided informative features for further examination. These included physicochemical features associated with the Src-homology-3 binding domain, the Nef loop (including the AP-2 Binding region), and a cytokine-binding domain. Non-brain sequences from patients with HIV-associated neurological disease were frequently classified as brain, suggesting that the approach could indicate neurological risk using blood-derived virus or for the development of biomarkers for use in assay systems aimed at drug efficacy studies for the treatment of HIV-associated neurological diseases.


HIV Brain Neurological disease Nef protein Analytical classification tools Macrophages 


Funding information

This project was funded by the National Institutes of Health grants R01MH100984 and UM1CA181255 to Michael S. McGrath and 1U24MH100929 to Elyse J. Singer.

Compliance with ethical standards

Conflict of interest

Lamers S.L., Barbier A.E., Rodriguez C., Nolan D.J., and Rose R. are employed by Bioinfoexperts LLC; Fogel GB and Liu E are employed by Natural Selection Inc.

Supplementary material

13365_2017_586_MOESM1_ESM.docx (31 kb)
ESM 1 (DOCX 30.6 kb)


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Copyright information

© Journal of NeuroVirology, Inc. 2017

Authors and Affiliations

  • Susanna L. Lamers
    • 1
    Email author
  • Gary B. Fogel
    • 2
  • Enoch S. Liu
    • 2
  • Andrew E. Barbier
    • 1
  • Christopher W. Rodriguez
    • 1
  • Elyse J. Singer
    • 3
  • David J. Nolan
    • 1
  • Rebecca Rose
    • 1
  • Michael S. McGrath
    • 4
  1. 1.Bioinfoexperts LLCThibodauxUSA
  2. 2.Natural Selection, IncSan DiegoUSA
  3. 3.The University of CaliforniaLos AngelesUSA
  4. 4.The University of CaliforniaSan FranciscoUSA

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