HIV-1 Nef is released in extracellular vesicles derived from astrocytes- evidence for Nef-mediated neurotoxicity (Cell death & disease, 2017,12;8(1):e2542. doi: 10.1038) Infectious Disease組,Coordinator:張志鵬

報告日期: 2017/03/07
報告時間: 5:10/6:00
報告學生: 顏克倫
講評老師: 王憲威
附件下載: 下載[1617-1487727730-1.pdf] 

HIV-1 Nef is released in extracellular vesicles derived from astrocytes: evidence for Nef-mediated neurotoxicity

A Sami Saribas, Stephanie Cicalese, Taha Mohseni Ahooyi, Kamel Khalili, Shohreh Amini and Ilker Kurdet Sariyer *

Cell Death and Disease 2017 Jan 12;8(1):e2542..

Speaker: Ko-Lun, Yen (顏克倫)             Time: 17:10~18:00, Mar, 07, 2017

Commentator: Dr. Shainn-Wei Wang(王憲威 教授) Place: Room 602

Abstract:

Human immunodificiency virus (HIV)-associated neurocognitive disorders (HANDs) is now the most common form of young-age dementia globally1, it even remains as the most common disorders ,in the individuals who (are) introduced with combined anti-retroviral therapies (cARTs). Anti-retroviral therapies have declined approximately 75% severity of neurological disease of HAND. However, it did not completely prevent the more severe form of HAND, HIV-1 associated dementia (HAD), furthermore, the prevalence of HANDs continues at high rates, between 15% and 50%, and in several cohorts appears almost resistant to anti-retroviral therapies2. Nevertheless, how neurocognitive performance is affected, even when HIV viremia is controlled still remained unknown. Nef is a viral protein which was expressed abundantly in astrocytes of HIV-1 infected brain, it has also been suggested to play a role in neuronal toxicity and the pathogenesis of HAND, but the extent of its effects in the central nervous system (CNS) remains unclear. To explore its effect in CNS, the author expressed HIV-1 Nef in prmary human fetal astrocytes (PHFAs) using an adenovirus, they found that HIV-1 Nef can be released in extracellular vesicles (EVs) derived from PHFA cells, and implied that the autophagy signaling might play a novel role in the release of HIV-1 Nef-containing EVs by treating with autophagy activators and inhibitors. Next, the author investigated the neurotoxic effect of Nef-carrying EVs, the results showed that after primary human fetal neurons (PHFN) was treated with Nef-carrying EVs, the oxidative stress increased and the intracellular expression of HIV-1 Nef caused axonal and neurite degeneration by decreasing the levels of phospho-tau protein in PHFN. In addition, the functional neuronal action potential, assessed by multielectrode array, was also been suppressed. Integrated above, these data suggest that HIV-1 Nef can be a threatful contributor to neurotoxicity which further leads to HAND in HIV-1 infected patients.

Reference:

  1. Wright EJ, Nunn M, Joseph J, et al. NeroAIDS in the Asia Pacific Region. J Neuroviral 2008; Nov 27:1-9.
  2. McArthur JC, Hoover DR, Bacellar H, et al. Dementia in AIDS patients: incidence and risk factors. Neurology 1993;43:2245-2252.