Daily Respiratory Research Analysis
Top respiratory research today highlights a scalable dual-humanized mouse model using cryopreserved human lung tissue that enables infection and immune profiling of all four common cold coronaviruses, a mechanistic study uncovering an epigenetic lncRNA (MIR100HG)-UPF1-NRF2 axis driving oxidative stress and immune remodeling in pulmonary hypertension, and a curated antiviral antibody database (MAAD) bridging sequence-structure-function to accelerate rational antibody design across coronaviruses,
Summary
Top respiratory research today highlights a scalable dual-humanized mouse model using cryopreserved human lung tissue that enables infection and immune profiling of all four common cold coronaviruses, a mechanistic study uncovering an epigenetic lncRNA (MIR100HG)-UPF1-NRF2 axis driving oxidative stress and immune remodeling in pulmonary hypertension, and a curated antiviral antibody database (MAAD) bridging sequence-structure-function to accelerate rational antibody design across coronaviruses, influenza, and RSV.
Research Themes
- Scalable humanized preclinical models for respiratory viruses
- Epigenetic regulation and oxidative stress in pulmonary vascular remodeling
- Rational antibody design enabled by integrated sequence-structure-function resources
Selected Articles
1. A Lung-Immune Dual-Humanized Mouse Using Cryopreserved Tissue Enables Infection and Immune Profiling of Human Common Cold Coronaviruses.
This study establishes a lung-immune dual-humanized mouse model using cryopreserved human fetal lung tissue, enabling robust infection by 229E, NL63, OC43, and HKU1. The platform validates Paxlovid efficacy against HKU1, reveals distinct phenotypes of human immune cells in implants versus native lungs, and demonstrates virus-specific T-cell responses and SARS-CoV-2 cross-reactivity after HKU1 infection.
Impact: Provides a scalable, ethically practical humanized lung model using cryopreserved tissues to study human-tropic coronaviruses and evaluate therapeutics and cross-immunity. It overcomes key barriers limiting CCCoV research and informs pan-coronavirus vaccine strategies.
Clinical Implications: While preclinical, this model enables realistic testing of antivirals and vaccination strategies for human-tropic respiratory coronaviruses and helps anticipate cross-protection patterns relevant to clinical vaccine design.
Key Findings
- Optimized transplantation of cryopreserved human fetal lung tissue improved engraftment and supported robust infection by 229E, NL63, OC43, and HKU1.
- Validated therapeutic efficacy of Paxlovid against HKU1 in the dual-humanized model.
- Identified phenotypic differences of human immune cells between native mouse lungs and human lung implants in dual-humanized mice.
- Demonstrated virus-specific T-cell responses and SARS-CoV-2 cross-reactivity after HKU1 infection.
Methodological Strengths
- Use of cryopreserved human fetal lung tissue enabling scalable, logistics-friendly humanization.
- Dual humanization (lung and immune system) with multi-virus infection validation and antiviral testing.
Limitations
- Preclinical mouse model may not fully recapitulate human lung architecture and long-term immune dynamics.
- Reliance on fetal human tissues and specific engraftment conditions may limit generalizability across labs.
Future Directions: Leverage the platform to test pan-coronavirus vaccines, broaden antiviral validation, and dissect age- and comorbidity-related immune interactions across respiratory viruses.
2. Epigenetically activated MIR100HG regulates UPF1-mediated oxidative stress to promote pulmonary vascular immune microenvironment remodeling.
The authors identify MIR100HG as a hypoxia-induced, epigenetically activated lncRNA in PH that binds UPF1 to modulate its interaction with NRF2 mRNA, thereby dampening antioxidant responses and amplifying oxidative stress. This promotes PASMC proliferation and macrophage activation via IBSP-ITGAV signaling, remodeling the pulmonary vascular immune microenvironment in vitro and in vivo.
Impact: Reveals a previously unrecognized MIR100HG–UPF1–NRF2 axis linking epigenetic regulation to oxidative stress and immune remodeling in PH, opening a mechanistically grounded therapeutic and biomarker avenue.
Clinical Implications: Suggests MIR100HG and its interaction with UPF1/NRF2 as candidate biomarkers and targets to modulate oxidative stress and immune dysregulation in pulmonary hypertension.
Key Findings
- MIR100HG was identified by ChIP-seq as a hypoxia-induced lncRNA with chromatin remodeling features in PASMCs.
- RELA (NF-κB p65) upregulates MIR100HG; MIR100HG binds UPF1 and modulates UPF1 binding to NRF2 mRNA, reducing NRF2 transcription.
- Elevated MIR100HG amplifies oxidative stress, drives PASMC proliferation, and promotes macrophage activation via IBSP-ITGAV signaling.
- Single-cell analyses indicate MIR100HG-driven reshaping of the pulmonary vascular immune microenvironment under hypoxia.
Methodological Strengths
- Multi-omics and mechanistic validation including ChIP-seq, mass spectrometry, RNA pulldown, RIP, and single-cell analyses.
- In vitro and in vivo corroboration linking molecular interactions to cellular proliferation and immune remodeling.
Limitations
- Translational relevance requires validation in human PH tissues and longitudinal clinical cohorts.
- Specificity and safety of targeting MIR100HG/UPF1/NRF2 need evaluation to avoid off-target oxidative stress effects.
Future Directions: Validate MIR100HG as a biomarker/therapeutic target in human PH cohorts; develop modulators of the MIR100HG–UPF1 interaction; test combinatorial strategies restoring NRF2 signaling.
3. MAAD: Multidimensional Antiviral Antibody Database.
MAAD is a curated, standardized database integrating antibody, nanobody, and scFv data targeting Coronaviridae, Orthomyxoviridae, and Pneumoviridae. It links sequence, structure, and function with interactive modules (CDR/germline annotation, similarity, clustering, interface residue mapping, per-site entropy/mutation rates) to enable cross-pathogen comparisons and rational antibody design.
Impact: Provides an open, multidimensional resource that bridges sequence-structure-function, likely to accelerate antiviral antibody discovery and comparative analyses across major respiratory viruses.
Clinical Implications: By supporting rational antibody design and cross-pathogen insights, MAAD may shorten timelines for therapeutic antibody development against respiratory viruses and inform vaccine strategies.
Key Findings
- Introduces a standardized, curated database encompassing antibodies, nanobodies, and scFvs targeting coronaviruses, influenza, and RSV/hMPV.
- Provides interactive modules for CDR/germline annotation, similarity analysis, clustering, and structure-guided antigen-antibody interface mapping.
- Includes per-site entropy and mutation rate profiling to inform functional hotspots and escape-prone residues.
- Enables systematic cross-pathogen comparison to facilitate rational antibody design.
Methodological Strengths
- Standardized curation with integrated analytical modules linking sequence, structure, and function.
- Cross-pathogen scope covering three high-impact respiratory virus families.
Limitations
- Relies on available public datasets which may have biases or gaps across pathogens and epitopes.
- Prospective benchmarking with experimental validation is needed to quantify predictive utility.
Future Directions: Expand to additional pathogens and integrate experimental benchmarking; develop AI-assisted design pipelines leveraging MAAD’s multidimensional features.