Amyloidogenic, neuroinflammatory and memory dysfunction effects of HIV-1 gp120

Young-Jung Lee,In Jun Yeo,Dong Young Choi,Dong Ju Son,Jin Tae Hong,Jaesuk Yun,Sang-Bae Han

doi:10.1007/s12272-021-01340-8

Abstract

Human immunodeficiency virus 1 (HIV-1) infection can cause several HIV-associated neurocognitive disorders a variety of neurological impairments characterized by the loss of cortical and subcortical neurons and decreased cognitive and motor function. HIV-1 gp120, the major envelope glycoprotein on viral particles, acts as a binding protein for viral entry and is known to be an agent of neuronal cell death. To determine the mechanism of HIV-1 gp120-induced memory dysfunction, we performed mouse intracerebroventricular (i.c.v.) infusion with HIV-1 gp120 protein (300 ng per mouse) and investigated memory impairment and amyloidogenesis. Infusion of the HIV-1 gp120 protein induced memory dysfunction, which was evaluated using passive avoidance and water maze tests. Infusion of HIV-1 gp120 induced neuroinflammation, such as the release of iNOS and COX-2 and the activation of astrocytes and microglia and increased the mRNA and protein levels of IL-6, ICAM-1, M-CSF, TIM, and IL-2. In particular, we found that the infusion of HIV-1 gp120 induced the accumulation of amyloid plaques and signs of elevated amyloidogenesis, such as increased expression of amyloid precursor protein and BACE1 and increased β-secretase activity. Therefore, these studies suggest that HIV-1 gp120 may induce memory impairment through Aβ accumulation and neuroinflammation.

Highlights

Alzheimer’s disease (AD) is the most common cause of dementia, accounting for 50–75% of all cases (Ferri et al 2009; Lee et al 2010) and the most common neurological complication
Significant differences between Human immunodeficiency virus 1 (HIV-1) gp120injected and control mice due to the memory impairment effect were seen on day two, and the impairment effect persisted for 5 days in the water maze test
The most important finding in this study was that administration of the HIV-1 gp120 protein induced memory impairment as well as amyloidogenesis and neuroinflammation in the mouse brain

Summary

Introduction

Alzheimer’s disease (AD) is the most common cause of dementia, accounting for 50–75% of all cases (Ferri et al 2009; Lee et al 2010) and the most common neurological complication. The underlying mechanism of AD development remains unclear, experimental data have demonstrated that neuroinflammation-mediated Aβ accumulation in the brain may initiate and/or contribute to the process of AD development (Lee et al 2010; Choi et al 2012; Shadfar et al 2015). It is well–known that viral proteins can activate macrophages, astrocytes and microglial cells that lead to the production of inflammatory molecules, further damaging neurons (Kaul et al 2001). It has been reported that HIV-1 gp120, a fragment proteolytically cleaved from the Env protein, can activate

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Conclusion