Prediction and analysis of human-herpes simplex virus type 1 protein-protein interactions by integrating multiple methods

Abstract Background: Herpes simplex virus type 1 (HSV-1) is a ubiquitous infectious pathogen that widely affects human health. To decipher the complicated human-HSV-1 interactions, a comprehensive protein-protein interaction (PPI) network between human and HSV-1 is highly demanded. Results: To complement experimental identification of human-HSV-1 PPIs, we developed an integrative strategy to predict proteome-wide PPIs between human and HSV-1. For each human-HSV-1 protein pair, four popular PPI inference methods, including interolog mapping, the domain-domain interaction-based method, domain-motif interaction-based method and machine learning-based method, were optimally implemented and employed to generate four interaction probability scores, and then these four scores were further integrated into a final probability score. As a result, a comprehensive high-confidence PPI interaction network between human and HSV-1 was established, which covers 10,432 interactions between 4,546 human proteins and 72 HSV-1 proteins. Functional and network analyses of the HSV-1 targeting proteins in the context of human interactome can recapitulate the known knowledge regarding the HSV-1 replication cycle, supporting the overall reliability of the predicted PPI network. Considering that HSV-1 infections are implicated in encephalitis and neurodegenerative diseases, we focused on exploring the biological significance of brain-specific human-HSV-1 PPIs. In particular, the predicted interactions between HSV-1 proteins and Alzheimer's-disease-related proteins were intensively investigated. Conclusions: The current work can provide testable hypotheses to assist mechanistic understanding of the human-HSV-1 relationship as well as the discovery of anti-HSV-1 pharmaceutical targets. To make the predicted PPI network and the datasets freely accessible to the scientific community, a user-friendly database browser has been released at http://www.zzdlab.com/HintHSV/index.php. Keywords: Human-virus interaction, Protein-protein interaction, Prediction, Herpes simplex virus type 1, Alzheimer's disease