Abstract

BackgroundHerpes 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.MethodsTo 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.ResultsAs 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.ConclusionThe 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.

Highlights

  • Herpes simplex virus type 1 (HSV-1) is a neurotropic, enveloped, and double-stranded linear DNA virus [1,2,3,4]

  • Due to similarity in the methodologies, the domain-domain interaction (DDI) achieved relatively more consistent protein-protein interaction (PPI) prediction results compared to the interolog mapping (IM) and the domainmotif interaction (DMI)

  • Taking the number of experimentally validated human-HIV-1 PPIs as a reference, 100 – 200 interactions with human proteins were identified for each HIV-1 protein in some high-throughput experimental studies [31]

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Summary

Introduction

Herpes simplex virus type 1 (HSV-1) is a neurotropic, enveloped, and double-stranded linear DNA virus [1,2,3,4]. More fundamental research efforts are required to decipher the complicated human-HSV-1 interactions to provide hints for developing novel prophylactic or therapeutic methods against viral infections. 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: 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. 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. 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

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