Evolution of proteomics technologies for understanding respiratory syncytial virus pathogenesis

Abstract

Introduction: Respiratory syncytial virus (RSV) is a major human pathogen associated with long term morbidity. RSV replication occurs primarily in the epithelium, producing a complex cellular response associated with acute inflammation and long-lived changes in pulmonary function and allergic disease. Proteomics approaches provide important insights into post-transcriptional regulatory processes including alterations in cellular complexes regulating the coordinated innate response and epigenome. Areas covered: Peer-reviewed proteomics studies of host responses to RSV infections and proteomics techniques were analyzed. Methodologies identified include 1)." bottom-up" discovery proteomics, 2). Organellar proteomics by LC-gel fractionation; 3). Dynamic changes in protein interaction networks by LC-MS; and 4). selective reaction monitoring MS. We introduce recent developments in single-cell proteomics, top-down mass spectrometry, and photo-cleavable surfactant chemistries that will have impact on understanding how RSV induces extracellular matrix (ECM) composition and airway remodeling. Expert opinion: RSV replication induces global changes in the cellular proteome, dynamic shifts in nuclear proteins, and remodeling of epigenetic regulatory complexes linked to the innate response. Pathways discovered by proteomics technologies have led to deeper mechanistic understanding of the roles of heat shock proteins, redox response, transcriptional elongation complex remodeling and ECM secretion remodeling in host responses to RSV infections and pathological sequelae.

Cooperative interaction of interferon regulatory factor -1 and bromodomain—containing protein 4 on RNA polymerase activation for intrinsic innate immunity

“…In response to RSV infection, the BRD4 CRC is recruited to the intrinsic IIR and epithelial plasticity genes. RSV infection increases ~100 proteins to bind the BRD4 complex ( 64 , 77 ). Through these associated proteins, BRD4 plays multiple functional roles in the coordinate genome innate response, including transcriptional elongation, stimulating enhancer remodeling, and mediating alternative mRNA splicing ( 65 ).…”

Bromodomain-containing Protein 4 regulates innate inflammation via modulation of alternative splicing

“…Significant improvements in proteomics technologies, particularly focused towards sensitivity and dynamic range, will be essential for comprehensive multi-omic quantitation of gene products. Furthermore, both short-read RNA-sequencing and shotgun proteomics use short, fragmented sequences as proxy for whole-transcript/protein abundance ( 99 , 103 ). This approach, while robust for whole-protein quantitation, cannot comprehensively identify and quantify all possible transcript variants and proteoforms ( 104 ).…”

Bromodomain-containing Protein 4 Regulates Innate Inflammation in Airway Epithelial Cells via Modulation of Alternative Splicing

“…Significant improvements in proteomics technologies, particularly focused towards sensitivity and dynamic range, will be essential for comprehensive multi-omic quantitation of gene products. Furthermore, both short-read RNA-sequencing and shotgun proteomics use short, fragmented sequences as proxy for whole-transcript/protein abundance [70, 74]. This approach, while robust for overall quantitation, can not comprehensively identify and quantify all possible transcript variants and proteoforms [75].…”