A network view of human immune system and virus-human interaction

The immune system is highly networked and complex, which is continuously changing as encountering old and new pathogens. However, reductionism-based researches do not give a systematic understanding of the molecular mechanism of the immune response and viral pathogenesis. Here, we present HUMPPI-2022, a high-quality human protein-protein interaction (PPI) network, containing > 11,000 protein-coding genes with > 78,000 interactions. The network topology and functional characteristics analyses of the immune-related genes (IRGs) reveal that IRGs are mostly located in the center of the network and link genes of diverse biological processes, which may reflect the gene pleiotropy phenomenon. Moreover, the virus-human interactions reveal that pan-viral targets are mostly hubs, located in the center of the network and enriched in fundamental biological processes, but not for coronavirus. Finally, gene age effect was analyzed from the view of the host network for IRGs and virally-targeted genes (VTGs) during evolution, with IRGs gradually became hubs and integrated into host network through bridging functionally differentiated modules. Briefly, HUMPPI-2022 serves as a valuable resource for gaining a better understanding of the composition and evolution of human immune system, as well as the pathogenesis of viruses.