Using Aqueous Humor Proteomics to Investigate Intraocular Herpesvirus Infections

Herpesviruses cause vision-threatening viral anterior uveitis (VAU) and acute retinal necrosis (ARN). This study employed aqueous humor (AH) proteomics to investigate the host response and pathological mechanisms in herpesvirus-induced uveitis. AH samples from patients with VAU caused by herpes simplex virus types 1 and 2 (HSV-1/2), varicella-zoster virus (VZV), and cytomegalovirus (CMV), as well as from patients with VZV-associated ARN, were analyzed using SWATH-MS. A spectral library of 558 proteins was established for quantitative analysis. The results revealed a core pathogenic signature common to all viral uvieits, characterized by upregulated innate immune and inflammatory pathways (e.g., complement and coagulation cascades, JAK-STAT, TNF-α, NF-κB) and downregulated homeostatic pathways (e.g., negative regulation of Wnt signaling, synapse organization). Despite these shared features, each virus exhibited distinct proteomic profiles. HSV-1 was associated with robust adaptive immunity (MHC class I presentation), while HSV-2 was linked to acute-phase response and Trail-mediated apoptosis.