CD8A and major depressive disorder: Furthermore, hypothalamic-pituitary-adrenal (HPA) axis dysregulation contributes to this mechanism: cortisol abnormalities from HPA axis hyperactivity suppress CD8+ T-cell function, essential for controlling latent viral reactivation.[58] Cortisol levels correlate positively with stress intensity and depression severity,[59] while chronic stress-induced HPA hyperactivity has been shown to increase latent HSV-1 reactivation in animal models.[60]