The landscape of human proteins interacting with viruses and other pathogens

Area of Science:

• Bioinformatics
• Systems Biology
• Infectious Disease Research

Background:

• Millions die annually from infectious diseases, yet pathogen-host interactions remain incompletely understood.
• Key questions persist regarding the properties and functional classes of human proteins targeted by pathogens.
• Identifying common infection pathways exploited by multiple pathogens is crucial for understanding disease mechanisms.

Purpose of the Study:

• To conduct the first comprehensive study of the human protein interaction landscape with pathogens.
• To integrate human-pathogen protein-protein interactions (PPIs) from diverse public databases.
• To analyze pathogen strategies for subverting human cellular processes.

Main Methods:

• Integrated human-pathogen PPI data for 190 pathogen strains from seven public databases.
• Analyzed 10,477 human-pathogen PPIs, predominantly for viral and human-HIV systems.
• Identified human protein hubs and bottlenecks targeted by both viral and bacterial pathogens.

Main Results:

• Both viral and bacterial pathogens preferentially interact with human protein hubs and bottlenecks.
• Constructed distinct sets of human proteins interacting with bacterial, viral, and multi-pathogen infections.
• Discovered enriched Gene Ontology functions including cell cycle regulation, nuclear transport, and immune response in pathogen-interacting proteins.

Conclusions:

• This study provides the first global overview of pathogen strategies for hijacking human cellular machinery.
• Understanding these interaction networks offers insights into infection mechanisms and potential therapeutic targets.
• The findings highlight conserved host-pathogen interaction principles across diverse infectious agents.