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Nef exosomes isolated from the plasma of individuals with HIV-associated dementia (HAD) can induce Aβ1–42 secretion in SH-SY5Y neural cells

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Abstract

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.

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Acknowledgments

NIMHD G12 MD007602, U54MD008149 NIAID R21AI095150, CFAR P30AI050409 (MP, VB) NINDS/NIH U54NS43049, NIMH/NIH R21MH68173, and NIMHD/NIH U54MD007584 (BS)

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, 720 Westview Dr. SW, Atlanta, GA, 30310, USA

    Mahfuz B. Khan, Michelle J. Lang, Ming-Bo Huang, Vincent C. Bond & Michael D. Powell

  2. Department of Immunology Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA

    Andrea Raymond

  3. Departments of Tropical Medicine, Medical Microbiology and Pharmacology and Pediatrics, University of Hawaii, John A. Burns School of Medicine, Honolulu, HI, 96813, USA

    Bruce Shiramizu

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  1. Mahfuz B. Khan
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  2. Michelle J. Lang
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  7. Michael D. Powell
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Correspondence to Michael D. Powell.

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Khan, M.B., Lang, M.J., Huang, MB. et al. Nef exosomes isolated from the plasma of individuals with HIV-associated dementia (HAD) can induce Aβ1–42 secretion in SH-SY5Y neural cells. J. Neurovirol. 22, 179–190 (2016). https://doi.org/10.1007/s13365-015-0383-6

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  • DOI: https://doi.org/10.1007/s13365-015-0383-6

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