Internal Medicine Department, Texas Tech University Health Sciences Center, 3601 4th Street, Lubbock, TX 79430, USA.
Garrison Institute on Aging, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.
Int J Mol Sci. 2022 May 15;23(10):5514. doi: 10.3390/ijms23105514.
Despite successful virologic control with combination antiretroviral therapy (cART), about half of people living with the human immunodeficiency virus-1 (HIV) develop an HIV-associated neurocognitive disorder (HAND). It is estimated that 50% of individuals who are HIV-positive in the United States are aged 50 years or older. Therefore, a new challenge looms as individuals living with HIV increase in age. There is concern that Alzheimer's disease (AD) may become prevalent with an earlier onset of cognitive decline in people living with HIV (PLWH). Clinical data studies reported the presence of AD biomarkers in PLWH. However, the functional significance of the interaction between HIV or HIV viral proteins and AD biomarkers is still not well studied. The main goal of the present study is to address this knowledge gap by determining if the HIV envelope glycoprotein 120 (HIV-gp120) can affect the cognitive functions in the Tau mouse AD model. Male Tau and age-matched, wild-type (WT) control mice were treated intracerebroventricularly (ICV) with HIV-gp120. The animals were evaluated for cognitive function using a Y-maze. We found that HIV-gp120 altered cognitive function in Tau mice. Notably, HIV-gp120 was able to promote a cognitive decline in transgenic Tau (P301L) mice compared to the control (HIV-gp120 and WT). We provide the first in vivo evidence of a cognitive interaction between an HIV viral protein and Tau mice.
尽管联合抗逆转录病毒疗法 (cART) 可成功控制病毒，但仍有约一半的人类免疫缺陷病毒 1 (HIV) 感染者会出现与 HIV 相关的认知障碍 (HAND)。据估计，美国 50%的 HIV 阳性人群年龄在 50 岁或以上。因此，随着 HIV 感染者年龄的增长，新的挑战迫在眉睫。人们担心阿尔茨海默病 (AD) 可能会随着 HIV 感染者认知能力下降的提前出现而变得普遍。临床数据研究报告了 AD 生物标志物在 HIV 感染者中的存在。然而，HIV 或 HIV 病毒蛋白与 AD 生物标志物之间相互作用的功能意义仍未得到充分研究。本研究的主要目的是通过确定 HIV 包膜糖蛋白 120 (HIV-gp120) 是否会影响 Tau 小鼠 AD 模型中的认知功能来解决这一知识空白。雄性 Tau 和年龄匹配的野生型 (WT) 对照小鼠通过脑室内 (ICV) 给予 HIV-gp120 治疗。使用 Y 迷宫评估动物的认知功能。我们发现 HIV-gp120 改变了 Tau 小鼠的认知功能。值得注意的是，与对照（HIV-gp120 和 WT）相比，HIV-gp120 能够促进转染 Tau（P301L）小鼠的认知下降。我们提供了 HIV 病毒蛋白与 Tau 小鼠之间存在认知相互作用的第一个体内证据。
