Proteomics analysis of viral infection in neurons

ABSTRACT: Endemic viral infections with low pathogenicity are often overlooked due to their mild symptoms, yet they can exert long-term effects on cellular function and contribute to disease pathogenesis. While viral infections have been implicated in neurodegenerative disorders, their impact on the neuronal proteome remains poorly understood. Here, we differentiated human induced pluripotent stem cells (KOLF2.1J) into mature neurons to investigate virus-induced proteomic changes following infection with five neurotropic endemic human viruses: Herpes simplex virus 1 (HSV-1), Human coronavirus 229E (HCoV-229E), Epstein-Barr virus (EBV), Varicella-Zoster virus (VZV), and Influenza A virus (H1N1). Given that these viruses can infect adults and have the potential to cross the placental barrier, their molecular impact on neurons may be relevant across the lifespan. Using mass spectrometry-based proteomics with a customized library for simultaneous detection of human and viral proteins, we confirmed successful infections and identified virus-specific proteomic signatures. Notably, virus-induced protein expression changes converged on key neuronal pathways, including those associated with neurodegeneration. Gene co-expression network analysis revealed virus-specific protein modules linked to Alzheimer’s and Parkinson’s disease pathways. Remarkably, several viral-induced proteomic alterations overlapped with changes observed in postmortem Alzheimer’s patient brains, suggesting a mechanistic connection between viral exposure and neurodegenerative disease progression. These findings provide molecular insights into how common viral infections perturb neuronal homeostasis and may contribute to neurodegenerative pathology, highlighting the need to consider endemic viruses as potential environmental risk factors in neurological disorders.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Yue Andy Qi  

LAB HEAD: Yue Andy Qi

PROVIDER: PXD061286 | Pride | 2026-06-23

REPOSITORIES: Pride