Synergy between HA cleavage site sequence and NA-mediated plasminogen recruitment as a virulence mechanism for low-pathogenic avian influenza.
mBio·
- DOI
- 10.1128/mbio.02466-25
- PMID
- 41744684
- PMCID
- PMC13059709
- OpenAlex
- W7131650060
- Study type
- Journal article
- Publisher
- Publisher unavailable
- Article type
- journal-article
- Integrity
- current
Why this research matters now
Characterizing these protein interactions establishes a molecular baseline for evaluating the threat level of emerging avian influenza variants. Such insights may strengthen predictive modeling efforts aimed at safeguarding commercial poultry operations from sudden pathogenic shifts.
Structured evidence summary
Research question
The investigation examines how specific amino acid variations in viral surface proteins influence the capacity of low-pathogenic avian influenza strains to trigger severe illness and disseminate within poultry hosts.
Study design
Researchers employed a reverse genetics platform to engineer wild-type and modified viral isolates, then evaluated their behavior across multiple avian cell cultures and chicken organoid models. Experimental validation extended to embryonic infection assays and computational screening of publicly available viral sequences.
Population and setting
The primary isolate originated from poultry experiencing an unexplained mortality event in Belgium during 2019. Subsequent laboratory evaluations utilized diverse avian tissue lines, organotypic chicken models, and developing avian embryos.
Main findings
A distinct neuraminidase residue enables binding to host plasminogen, which collaborates with an unconventional hemagglutinin cleavage region to permit enzyme-independent viral activation. Introducing standard consensus sequences at these positions substantially diminished proteolytic processing, replication efficiency, and systemic distribution in laboratory models. Computational mapping identified additional circulating lineages harboring similar molecular signatures, indicating a wider pattern of unexpected virulence among otherwise mild strains.
Public-health relevance
Characterizing these protein interactions establishes a molecular baseline for evaluating the threat level of emerging avian influenza variants. Such insights may strengthen predictive modeling efforts aimed at safeguarding commercial poultry operations from sudden pathogenic shifts.
Important limitations
The experimental framework relies on engineered mutations and controlled laboratory environments that may not capture the full complexity of natural host immunity or environmental transmission routes. Consequently, observed replication patterns require further validation under field conditions.
GIDS interpretation
The described molecular pathways highlight specific genetic markers that could theoretically inform future genomic tracking protocols. These findings offer a conceptual foundation for variant prioritization without implying integration into current operational monitoring systems.
Related GIDS surveillance
Literature context does not validate, explain, or change a surveillance signal. Exact and contextual relationships are shown separately.
Evidence relationships
This article has 8 auditable classifier relationships to diseases, places, topics, and study design.