HSV-1 hijacks mitochondrial dynamics: potential molecular mechanisms linking viral infection to neurodegenerative disorders.

Abstract

Herpes simplex virus type 1 (HSV-1), a neurotropic virus, hijacks the critical neuronal organelle-mitochondria-to establish lifelong latent infection and potentially accelerate neurodegenerative pathologies. Research indicates that HSV-1 infection disrupts mitochondrial dynamics, impairs its bioenergetic function, and compromises interorganellar communication. This disruption is primarily achieved through the degradation of mitochondrial DNA (mtDNA) and the functional alteration of key proteins, leading to excessive production of reactive oxygen species (ROS), intracellular calcium dysregulation, and abnormal energy metabolism. These alterations not only diminish cellular energy production and exacerbate oxidative damage but also readily trigger neuronal cell death. Crucially, the virus specifically interferes with mitochondrial-endoplasmic reticulum contact sites (MERCs) to evade immune surveillance while simultaneously promoting its own replication. In severe encephalitis, mitochondrial damage is closely associated with neuroinflammation. For Alzheimer's disease (AD), HSV-1 may synergize with amyloid-beta pathology through ROS and viral proteins (such as glycoprotein B (gB) and glycoprotein I (gI)), exacerbating disease progression. Paradoxically, HSV-1 also inhibits immediate cell death to sustain host cell survival, facilitating latent viral reactivation. Research elucidating how the virus exploits mitochondria for pathogenesis suggests that future therapeutic strategies could combine classical antiviral drugs with agents that protect mitochondrial function (e.g., antioxidants). This combined approach holds promise for combating acute infection and potentially mitigating the progression of associated neurodegenerative diseases.