Nef exosomes isolated from the plasma of individuals with HIV-associated dementia (HAD) can induce Aβ(1-42) secretion in SH-SY5Y neural cells

J Neurovirol. 2016 Apr;22(2):179-90. doi: 10.1007/s13365-015-0383-6. Epub 2015 Sep 25.


In the era of combined antiretroviral therapy (CART), many of the complications due to HIV-1 infection have diminished. One exception is HIV-associated neurocognitive disorder (HAND). HAND is a spectrum of disorders in cognitive function that ranges from asymptomatic disease to severe dementia (HAD). The milder form of HAND has actually remained the same or slightly increased in prevalence in the CART era. Even in individuals who have maintained undetectable HIV RNA loads, viral proteins such as Nef and Tat can continue to be expressed. In this report, we show that Nef protein and nef messenger RNA (mRNA) are packaged into exosomes that remain in circulation in patients with HAD. Plasma-derived Nef exosomes from patients with HAD have the ability to interact with the neuroblastoma cell line SH-SY5Y and deliver nef mRNA. The mRNA can induce expression of Nef in target cells and subsequently increase expression and secretion of beta-amyloid (Aβ) and Aβ peptides. Increase secretion of amyloid peptide could contribute to cognitive impairment seen in HAND.

Keywords: Amyloid; Combination antiretroviral therapy; HIV; HIV-associated neurocognitive disorders; Nef.

Publication types

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

MeSH terms

  • AIDS Dementia Complex / blood*
  • AIDS Dementia Complex / drug therapy
  • AIDS Dementia Complex / physiopathology
  • AIDS Dementia Complex / virology
  • Adult
  • Aged
  • Amyloid beta-Peptides / biosynthesis*
  • Amyloid beta-Peptides / genetics
  • Amyloid beta-Peptides / metabolism
  • Anti-HIV Agents / therapeutic use
  • Cell Line, Tumor
  • Exosomes / metabolism*
  • Exosomes / pathology
  • Female
  • Gene Expression Regulation
  • HEK293 Cells
  • HIV-1 / drug effects
  • HIV-1 / physiology
  • Humans
  • Male
  • Middle Aged
  • Neurons / metabolism
  • Neurons / pathology
  • Peptide Fragments / biosynthesis*
  • Peptide Fragments / genetics
  • Peptide Fragments / metabolism
  • RNA, Messenger / biosynthesis*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Viral / blood*
  • Viral Load
  • nef Gene Products, Human Immunodeficiency Virus / genetics*
  • nef Gene Products, Human Immunodeficiency Virus / metabolism


  • Amyloid beta-Peptides
  • Anti-HIV Agents
  • Peptide Fragments
  • RNA, Messenger
  • RNA, Viral
  • amyloid beta-protein (1-42)
  • nef Gene Products, Human Immunodeficiency Virus
  • nef protein, Human immunodeficiency virus 1