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.

Methods: To complement the experimental identification of human-HSV-1 PPIs, an integrative strategy to predict proteome-wide PPIs between human and HSV-1 was developed. For each human-HSV-1 protein pair, four popular PPI inference methods, including interolog mapping, the domain-domain interaction-based method, the domain-motif interaction-based method, and the machine learning-based method, were optimally implemented to generate four interaction probability scores, which were further integrated into a final probability score.

Results: As a result, a comprehensive high-confidence PPI network between human and HSV-1 was established, covering 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 the brain-specific human-HSV-1 PPIs. In particular, the predicted interactions between HSV-1 proteins and Alzheimer’s-disease-related proteins were intensively investigated.

Conclusion: The current work can provide testable hypotheses to assist in the mechanistic understanding of the human-HSV-1 relationship and the anti-HSV-1 pharmaceutical target discovery. To make the predicted PPI network and the datasets freely accessible to the scientific community, a user-friendly database browser was released at http://www.zzdlab.com/HintHSV/index.php.

Graphical abstract

Keywords

human-virus interaction / protein-protein interaction / prediction / herpes simplex virus type 1 / Alzheimer’s disease

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SUPPLEMENTARY MATERIALS

The supplementary materials can be found online with this article at https://doi.org/10.1007/s40484-020-0222-5.

ACKNOWLEDGEMENTS

This work was supported by the National Key Research and Development Program of China (2017YFC1200205 to Z.Z. and 2017YFC1200204 to D.P.).

COMPLIANCE WITH ETHICS GUIDELINES

The authors Xianyi Lian, Xiaodi Yang, Jiqi Shao, Fujun Hou, Shiping Yang, Dongli Pan and Ziding Zhang declare that they have no competing interests. ƒThe article does not contain any human or animal subjects performed by any of the authors.

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