背景:新的证据表明,病毒感染可能有助于阿尔茨海默病(AD)的发病和/或进展。然而,它们的参与程度和特定病毒增加AD易感性风险的机制仍然难以捉摸.
方法:我们使用综合系统生物信息学方法来鉴定病毒介导的致病机制,其中单纯疱疹病毒1(HSV-1),人巨细胞病毒(HCMV),EB病毒(EBV)卡波西肉瘤相关疱疹病毒(KSHV),乙型肝炎病毒(HBV),丙型肝炎病毒(HCV),甲型流感病毒(IAV)和严重急性呼吸综合征冠状病毒2(SARS-CoV-2)可通过病毒-宿主蛋白-蛋白相互作用(PPI)促进AD发病。我们还探索了由疱疹病毒再激活导致的潜在协同致病作用(HSV-1,HCMV,和EBV)在急性SARS-CoV-2感染期间,潜在增加AD易感性。
结果:疱疹病毒科成员(HSV-1,EBV,KSHV,HCMV)影响AD相关过程,如淀粉样β(Aβ)形成,神经元死亡,和自噬。肝炎病毒(HBV,HCV)影响对细胞稳态和功能障碍至关重要的过程,它们还通过病毒宿主PPI影响小胶质细胞的激活.SARS-CoV-2感染期间HCMV的重新激活可能会促进神经变性的致命相互作用,通过对AD相关过程的协同致病作用,如对未折叠蛋白的反应,调节自噬,对氧化应激的反应,Aβ的形成。
结论:这些发现强调了病毒感染与AD发展之间的复杂联系。病毒通过共享和独特的机制影响与AD相关的过程,潜在影响AD易感性的变化。
BACKGROUND: Emerging evidence suggests that viral infections may contribute to Alzheimer\'s disease (AD) onset and/or progression. However, the extent of their involvement and the mechanisms through which specific viruses increase AD susceptibility risk remain elusive.
METHODS: We used an integrative systems bioinformatics approach to identify viral-mediated pathogenic mechanisms, by which Herpes Simplex Virus 1 (HSV-1), Human Cytomegalovirus (HCMV), Epstein-Barr virus (EBV), Kaposi Sarcoma-associated Herpesvirus (KSHV), Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), Influenza A Virus (IAV) and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) could facilitate AD pathogenesis via virus-host protein-protein interactions (PPIs). We also explored potential synergistic pathogenic effects resulting from herpesvirus reactivation (HSV-1, HCMV, and EBV) during acute SARS-CoV-2 infection, potentially increasing AD susceptibility.
RESULTS: Herpesviridae members (HSV-1, EBV, KSHV, HCMV) impact AD-related processes like amyloid-β (Aβ) formation, neuronal death, and autophagy. Hepatitis viruses (HBV, HCV) influence processes crucial for cellular homeostasis and dysfunction, they also affect microglia activation via virus-host PPIs. Reactivation of HCMV during SARS-CoV-2 infection could potentially foster a lethal interplay of neurodegeneration, via synergistic pathogenic effects on AD-related processes like response to unfolded protein, regulation of autophagy, response to oxidative stress, and Aβ formation.
CONCLUSIONS: These findings underscore the complex link between viral infections and AD development. Viruses impact AD-related processes through shared and distinct mechanisms, potentially influencing variations in AD susceptibility.