Towards a unified classification for human respiratory syncytial virus genotypes

Area of Science:

• Virology
• Phylogenetics
• Molecular Biology

Background:

• Human respiratory syncytial virus (HRSV) genotype classification has lacked consistent criteria since 1998, hindering inter-researcher data comparison.
• Previous methods for defining HRSV genotypes have yielded inconsistent conclusions.
• A unified approach is needed to standardize HRSV genotype classification.

Purpose of the Study:

• To review past HRSV genotype classification methods.
• To propose a novel, unified classification procedure for HRSV genotypes.
• To establish robust criteria for defining HRSV genotypes based on phylogenetic analysis.

Main Methods:

• Downloaded and analyzed over 12,000 complete HRSV genomes from GenBank, dividing them into HRSV-A and HRSV-B subgroups.
• Assessed phylogenetic signal in glycoprotein G and HVR2 regions, finding them insufficient for reliable reconstruction.
• Utilized whole-genome alignments, maximum likelihood phylogenetic trees, and patristic distances to define genotype criteria.

Main Results:

• Neither the HVR2 fragment nor the G gene provided sufficient phylogenetic signal for reliable HRSV genotype reconstruction.
• Whole-genome alignments were determined to be the most reliable method for HRSV genotype classification.
• Defined new criteria for HRSV genotypes: bootstrap support < 70% and maximum patristic distance ≤0.018 (HRSV-A) or ≤0.026 (HRSV-B).
• Identified 23 genotypes within HRSV-A and 6 genotypes within HRSV-B using the new criteria.
• Confirmed the robustness of the proposed method through subsampling analysis.

Conclusions:

• Whole-genome phylogenetic analysis provides a reliable basis for HRSV genotype classification.
• The proposed criteria offer a standardized and robust method for defining HRSV genotypes.
• This unified approach will enhance consistency and comparability in HRSV research globally.