Proteomic characteristics of cellular proteins from 16HBE cells with Coxsackievirus A10 infection by tandem mass tag (TMT) labeling-based quantitative proteomics reveals the potential effect of HMGB1 on viral replication

Abstract

Abstract Coxsackievirus A10 (CV-A10) is recognized as one of the most important pathogens associated with hand, foot, and mouth disease (HFMD) in young children under 5 years of age worldwide, and it can lead to fatal neurological complications. However, available commercial vaccines fail to protect against CV-A10. Therefore, the study of new protein targets against CV-A10 highlight the urgent need for the development of vaccine-based strategies. Currently, advances in proteomics have enabled a comprehensive understanding of host-pathogen interactions in recent years. Here, to study CV-A10-host interaction, a global quantitative proteomic analysis could help uncover the molecular determinants of host cellular proteins and excavate key host proteins following CV-A10 infection. Through tandem mass tagging (TMT)-based mass spectrometry, it was found that a total of 6615 host proteins were quantified, with 293 proteins being differentially regulated. To ensure the validity and reliability of the proteomics data, 3 randomly selected proteins were verified by Western blot analysis, and the results were consistent with the TMT results. Further functional analysis showed that the up-regulated and down-regulated proteins were individually enriched in diverse biological activities and signaling pathways, such as metabolic process, biosynthetic process, AMPK signaling pathway, Neurotrophin signaling pathway, MAPK signaling pathway, GABAergic synapse, and so on. Moreover, subsequent bioinformatics analysis further exhibited that these differentially expressed proteins contained distinct domains, localized in different subcellular components, and generated a complex network. Finally, it was also found that HMGB1 might be a key host factor to be involved in CV-A10 replication. In summary, our findings provided comprehensive insights into the proteomic profile during CV-A10 infection and added depth to our understanding of the relationship between CV-A10 and host cell, as well as also established a proteomic signature for this viral infection. Meanwhile, based on the effect of HMGB1 on CV-A10 replication, it might be regarded as a promising therapeutic target against CV-A10 infection.