| Computational Identification of Host-Pathogen Interaction Networks in Tick-Borne Viral Infections |
| Paper ID : 1125-IPCA5 (R1) |
| Authors |
|
Elina Khanehzar1, Fatemeh Shams1, Masoud Abedi2, Baran Rahmatian *3, Sonia Jafarinia4, Saman Moradian5, Zakkyeh Telmadarraiy6, Amirsajad Jafari7 11. Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran 2. Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, Iran 2Faculty of Veterinary Medicine, Shahid Bahonar University of Kerman, Kerman, Iran 3Faculty of Veterinary Medicine, Islamic Azad University of Urmia Branch, West Azerbaijan, Iran 4Faculty of Veterinary Medicine, Islamic Azad University of Karaj Branch, Alborz, Iran 5Faculty of Veterinary Medicine, Islamic Azad University of Babol Branch, Babol, Iran 61 Department of Medical Entomology and Vector Control, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran 2. Rahyan Novin Danesh (RND) University, Sari, Mazandaran, Iran 71. Department of Basic Sciences, School of Veterinary Medicine, Shiraz University, Shiraz, Iran
2. Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, Iran |
| Abstract |
| Ticks are dangerous vectors of deadly viral diseases, including Crimean-Congo hemorrhagic fever (CCHF) and Powassan virus, posing major global health risks. Key species like Hyalomma (found in Africa, Asia, and Europe) and Ixodes (dominant in North America) spread these infections, adapting easily to changing environments. Their complex life cycle—egg, larva, nymph, and adult—allows multiple transmission opportunities, with nymphs being especially dangerous due to their tiny size and prolonged, undetected feeding. Tick saliva contains immune-suppressing and anti-clotting compounds that help viruses evade host defenses and replicate efficiently. Climate change, deforestation, and growing host populations (e.g., deer, rodents) have expanded tick habitats, increasing infections. Hyalomma ticks aggressively seek hosts and spread CCHF, which has a 30% mortality rate, while Ixodes scapularis transmits Powassan virus, causing severe neurological damage. Diagnosing and treating these diseases is challenging due to overlapping symptoms like fever, hemorrhage, and encephalitis, as well as limited therapeutic options. Despite belonging to different viral families, these pathogens likely hijack common host cell pathways, aided by tick-derived factors. Understanding these shared mechanisms could reveal broad-spectrum antiviral targets, offering new strategies to combat the rising threat of tick-borne diseases. Identifying key host-pathogen interactions is crucial for developing effective treatments against these expanding infections. We employed an integrated bioinformatics approach to analyze protein-protein interaction (PPI) networks. First, the Pharos database (https://pharos.nih.gov/) was used to identify human proteins implicated in both viral infections. Next, a PPI network was constructed using STRING (https://string-db.org/) and analyzed in Cytoscape to identify key hub proteins based on network centrality metrics (degree and closeness centrality). Cytoscape network analysis identified highly connected hub proteins, including 14-3-3 family members (YWHAH, YWHAB, YWHAE), UBQLN2/3, and RAD23A/B, with key roles in cellular processes. Proteins like PCNA and UBC showed high betweenness centrality, acting as network bridges, while YWHAZ and SUMO3 exhibited functional robustness. YWHAH emerged as a top therapeutic candidate due to its dense interactions and stability. These findings highlight the power of network analysis in pinpointing critical proteins for antiviral targeting, though experimental validation is needed to confirm their roles in disease mechanisms and therapeutic potential. The computational identification of conserved host-pathogen interaction networks offers a promising strategy for addressing the growing threat of tick-borne viral infections. By targeting highly connected hub proteins like YWHAH, which are likely modulated by tick vector-mediated infection processes, we can develop host-directed antiviral therapies to disrupt the molecular mechanisms exploited by these pathogens. |
| Keywords |
| Bioinformatics, CCHFV, PPI, Drug discovery, Host-pathogen interactions |
| Status: Abstract Accepted |
