New anti-viral strategies at the respiratory tract interface

Airway epithelial cells are frontline sentinels that detect, restrict, and orchestrate immune responses to respiratory viruses. Beyond canonical interferon (IFN) signaling, recent work has uncovered layered epithelial-intrinsic defenses, including pattern recognition tuning (RIG-I/MDA5), RNA editing, metabolic and epigenetic control, and barrier/mucociliary mechanisms, that shape viral susceptibility and disease outcomes. High-resolution technologies such as single-cell and spatial multi-omics, alongside advanced ex vivo airway models (ALI cultures, organoids), now enable precise mapping of these antiviral programs across age, phenotype, and comorbidity contexts. Given that rhinovirus remains a leading trigger of asthma exacerbations, translating epithelial biology into targeted, safe, and durable interventions is an urgent clinical priority.This research topic aims at identifying new strategies to modulate interferon or other recently discovered anti-viral responses in airway epithelial cells to reduce susceptibility to viral infections, particularly Rhinovirus. By integrating cutting-edge technologies such as high-throughput sequencing and bioinformatics modeling, this research topic will propose innovative therapeutic interventions. The goal is to develop novel strategies for preventing asthma exacerbations triggered by viral infections, thereby improving patient outcomes We welcome contributions in the form of original research, review, mini review, case report, hypothesis and theory, perspective, both experimental and computational studies that cover, but are not limited to, following themes:- Modulation of type I/III IFN dynamics, signaling kinetics, and feedback control in health, asthma, and COPD;- Epithelial-intrinsic antiviral programs, including RIG-I/MDA5 calibration, ADAR/RNA editing, restriction factors, stress responses, metabolic and epigenetic regulation, and barrier/mucociliary and surfactant-mediated defenses;- Therapeutic concepts and delivery strategies such as small molecules, biologics, nucleic acid therapeutics (siRNA/ASO/mRNA), decoy receptors, innate immune agonists/antagonists, pro-resolving mediators, inhaled or epithelial-targeted delivery, and nanoparticle platforms;- Predictive modeling and integrative bioinformatics using single-cell and spatial transcriptomics, ATAC-seq, proteomics, and metabolomics for network inference, causal modeling, and biomarker discovery;- Disease contexts including rhinovirus pathogenesis, interactions with RSV, influenza, and SARS-CoV-2, age-specific and comorbidity-informed differences, exacerbation endotypes, and strategies for patient stratification;- Experimental systems and tools encompassing human ALI cultures, organoids, co-cultures, microphysiological platforms, in vivo models capturing epithelial–immune crosstalk, spatial imaging, and real-time infection tracking. Topic editors: Susetta Finotto, Tanima Bose Source: https://www.frontiersin.org/research-topics/79526/new-anti-viral-strategies-at-the-respiratory-tract-interface