随着针对人类免疫缺陷病毒(HIV)的联合抗逆转录病毒疗法(cART)的发展,极大地改善了HIV感染者的寿命,许多人现在正进入老年痴呆症(AD)样症状开始显现的黄金时代。已经表明,过度磷酸化的tau,已知的AD病理特征,早在30多岁时,HIV感染者的大脑就会过早增加,并且随着年龄的增长,其水平也会增加。这表明HIV感染可能导致加速的AD表型。然而,HIV感染是否会导致AD在大脑中更快地发展尚未完全确定。有趣的是,我们之前已经发现,病毒糖蛋白HIVgp120和猫免疫缺陷病毒(FIV)gp95通过cGMP依赖性激酶II(cGKII;也称为PRKG2)激活,在培养的海马神经元中诱导神经元过度兴奋.这里,我们使用培养的小鼠皮质神经元来证明HIVgp120和FIVgp95的存在足以增加细胞tau病理,包括细胞内tau过度磷酸化和tau释放到细胞外空间。我们进一步揭示了病毒糖蛋白诱导的细胞tau病理需要cGKII激活。一起来看,HIV感染可能通过cGKII激活加速AD相关tau病理。
As the development of combination antiretroviral therapy (cART) against human immunodeficiency virus (HIV) drastically improves the lifespan of individuals with HIV, many are now entering the prime age when Alzheimer\'s disease (AD)-like symptoms begin to manifest. It has been shown that hyperphosphorylated tau, a known AD pathological characteristic, is prematurely increased in the brains of HIV-infected individuals as early as in their 30s and that its levels increase with age. This suggests that HIV infection might lead to accelerated AD phenotypes. However, whether HIV infection causes AD to develop more quickly in the brain is not yet fully determined. Interestingly, we have previously revealed that the viral glycoproteins HIV gp120 and feline immunodeficiency virus (FIV) gp95 induce neuronal hyperexcitation via cGMP-dependent kinase II (cGKII; also known as PRKG2) activation in cultured hippocampal neurons. Here, we use cultured mouse cortical neurons to demonstrate that the presence of HIV gp120 and FIV gp95 are sufficient to increase cellular tau pathology, including intracellular tau hyperphosphorylation and tau release to the extracellular space. We further reveal that viral glycoprotein-induced cellular tau pathology requires cGKII activation. Taken together, HIV infection likely accelerates AD-related tau pathology via cGKII activation.