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Updated: Jun 6, 2026

Generation, Amplification, and Titration of Recombinant Respiratory Syncytial Viruses
Published on: April 4, 2019
Molecular Evolution in the Second Hypervariable Region of the G Gene for Human Respiratory Syncytial Virus Lineage
Yuqing Shi1, Zhen Zhu1, Jinhua Song1
1National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, NHC Key Laboratory of Medical Virology and Viral Disease, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention & Chinese Academy of Preventive Medicine, Beijing, China.
Introduction:
Human respiratory syncytial virus subgroup A (HRSV-A) lineage A.D is characterized by a unique 72-nucleotide duplication in the second hypervariable region of the G-gene (G-HVR2) and has become the predominant global circulating strain since 2010. Molecular evolutionary features of this region should be monitored.
Methods:
A global HRSV-A G-HVR2 sequence dataset (2010-2024) was assembled that included 144 Chinese sequences and the molecular characteristics and evolutionary patterns in lineage A.D were analyzed.
Results:
Molecular clock analysis based on G-HVR2 estimated that HRSV-A lineage A.D originated in 2006, with subsequent diversification into four distinct lineages. A.D.4 and A.D.5 were grouped as A.D.4/A.D.5. Lineages circulate globally with temporal fluctuations and sequential dominance shifts. The evolutionary rate of A.D was high, with the highest rate observed in A.D.4/A.D.5. Amino acid analysis indicated five shared, lineage-specific mutations in A.D.1 and A.D.4/A.D.5 that coincided with high-frequency mutation sites. Nine positively-selected sites were predicted across all lineages, three of which resided within the 72-nucleotide duplication. A.D.1 and A.D.4/A.D.5 lost conserved N- and O-glycosylation sites. A 72-nucleotide duplication in lineage A.D introduced two extra β-strands and two unique α-helical motifs relative to the prototype strain.
Conclusion:
Adaptive evolution in the G-HVR2 region of HRSV-A lineage A.D was evident, likely facilitating the rapid transmission of this lineage. Sustained monitoring of lineage-specific evolution in this region is critical for targeted prevention and control of HRSV infections.
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