Advertisement

 

 

HIV-1 counteracts an innate restriction by amyloid precursor protein resulting in neurodegeneration.

HIV-1 counteracts an innate restriction by amyloid precursor protein resulting in neurodegeneration.
Author Information (click to view)

Chai Q, Jovasevic V, Malikov V, Sabo Y, Morham S, Walsh D, Naghavi MH,


Chai Q, Jovasevic V, Malikov V, Sabo Y, Morham S, Walsh D, Naghavi MH, (click to view)

Chai Q, Jovasevic V, Malikov V, Sabo Y, Morham S, Walsh D, Naghavi MH,

Advertisement
Share on FacebookTweet about this on TwitterShare on LinkedIn

Nature communications 2017 11 158(1) 1522 doi 10.1038/s41467-017-01795-8

Abstract

While beta-amyloid (Aβ), a classic hallmark of Alzheimer’s disease (AD) and dementia, has long been known to be elevated in the human immunodeficiency virus type 1 (HIV-1)-infected brain, why and how Aβ is produced, along with its contribution to HIV-associated neurocognitive disorder (HAND) remains ill-defined. Here, we reveal that the membrane-associated amyloid precursor protein (APP) is highly expressed in macrophages and microglia, and acts as an innate restriction against HIV-1. APP binds the HIV-1 Gag polyprotein, retains it in lipid rafts and blocks HIV-1 virion production and spread. To escape this restriction, Gag promotes secretase-dependent cleavage of APP, resulting in the overproduction of toxic Aβ isoforms. This Gag-mediated Aβ production results in increased degeneration of primary cortical neurons, and can be prevented by γ-secretase inhibitor treatment. Interfering with HIV-1’s evasion of APP-mediated restriction also suppresses HIV-1 spread, offering a potential strategy to both treat infection and prevent HAND.

Submit a Comment

Your email address will not be published. Required fields are marked *

14 − three =

[ HIDE/SHOW ]