Respiratory Research Analysis

This study identifies MFSD6 as the cellular entry receptor for enterovirus D68 (EV‑D68), providing a molecular basis for host tropism and a tractable target to block viral attachment and entry. The discovery enables development of receptor-blocking therapeutics, decoys, and refined disease models for EV‑D68 and associated acute flaccid myelitis.

Impact: Discovery of a bona fide host receptor is paradigm-shifting—enabling direct host-directed antivirals, prophylactic decoys, and mechanistic studies that can rapidly translate into preventive or therapeutic strategies for a respiratory pathogen with neurologic sequelae.

Clinical Implications: MFSD6 offers a direct target for development of receptor-blocking antibodies or small molecules, decoy receptors, and risk stratification by tissue-expression profiling; these could reduce EV‑D68 infection or severity and inform AFM prevention strategies.

Using allergen inhalation models and lineage-tracing reporter mice, authors show that IgE class-switching occurs predominantly within the lung and that lung-resident memory B cells (likely IgG1-lineage MBCs) sustain airway IgE production. This reveals a local memory circuit that maintains allergic responses and suggests tissue-targeted interventions.

Impact: Reframes allergic airway pathophysiology by implicating tissue-resident B cells—rather than systemic IgE-only models—as central drivers of persistent IgE responses, opening new therapeutic avenues (local niche disruption, blocking class-switch locally).

Clinical Implications: Therapies that disrupt lung-resident memory B cell niches or inhibit local IgG1→IgE switching may offer durable control of asthma and allergic rhinitis beyond systemic anti-IgE approaches; translational work in human airway tissues is a priority.

Integrating deep mutational scanning (DMS), structure-based modeling, machine learning, and experimental validation, authors redesigned a clinical SARS‑CoV‑2 antibody (AZD3152) into a candidate (3152‑1142) with restored and broadened neutralization across contemporary and prospective escape variants, including XBB.1.5+F456L, and without newly identified vulnerability by DMS.

Impact: Provides a reproducible, preemptive blueprint for future-proofing monoclonal antibodies against rapidly evolving respiratory viruses, demonstrating how DMS + AI + structural design can be integrated into antibody lifecycle management.

Clinical Implications: Supports development pipelines that periodically update clinical antibodies by computational redesign to retain clinical utility across emerging variants; could preserve prophylactic/therapeutic options for immunocompromised patients.

Using in‑cell cryo‑electron tomography, the study directly visualized native structures and spatial organization of major mitochondrial respiratory complexes within intact cells, providing a structural framework to link supercomplex assembly with in vivo electron transfer and proton pumping efficiency.

Impact: Resolves a longstanding uncertainty by providing high‑resolution, native‑context structural data that underpin models of mitochondrial function and disease across respiratory medicine and beyond.

Clinical Implications: Although preclinical, the architecture map can inform hypotheses for mitochondrial disease mechanisms, biomarker discovery, and future strategies to modulate respiratory chain supercomplexes in lung disorders.

Multicenter translational work identifies a mechanistic axis linking Epstein–Barr virus (EBV) reactivation to MIS‑C via TGF‑β signaling, mapping immune pathways that connect prior viral exposures to post‑SARS‑CoV‑2 hyperinflammation and suggesting biomarkers and therapeutic targets along the TGF‑β axis.

Impact: Reframes MIS‑C pathogenesis by implicating a conserved, druggable host signaling pathway (TGF‑β) downstream of EBV exposure, creating translational opportunities for biomarker‑guided risk stratification and targeted immunomodulation.

Clinical Implications: Supports evaluation of EBV reactivation and TGF‑β–related immune signatures in suspected MIS‑C for risk stratification, and motivates early‑phase trials testing TGF‑β pathway modulation or EBV‑targeted antiviral approaches as adjuncts to current MIS‑C care.