Short G-Gene Sequencing Window Can Track Major HRSV Lineages, Study Finds

Human respiratory syncytial virus (HRSV) surveillance may not always require whole-genome sequencing, according to a new study published in BMC Infectious Diseases. The research shows that a short, well-established sequencing window within the viral G gene can reliably assign major HRSV lineages, offering a practical complement to whole-genome sequencing (WGS), particularly in resource-limited settings.

The study focuses on the second hypervariable region near the C-terminus of the G gene, known as HVR2-G. This region has been the standard target for HRSV genotyping in molecular epidemiology surveillance for nearly 28 years, and a large body of virological data has been accumulated from it. In recent years, however, WGS has been suggested as the preferred approach for classifying HRSV lineages because it offers the highest resolution, a shift that has raised questions about how older HVR2-G genotyping data should be interpreted alongside the newer WGS-defined lineage nomenclature.

Addressing that gap was the central aim of the study: to evaluate whether the HVR2-G sequencing window remains applicable for lineage classification and to integrate the previous HVR2-G genotypes with the new WGS-defined lineage nomenclature.

Methodologically, the researchers extracted the HVR2-G region from whole-genome sequences available in GenBank and downloaded lineage nomenclature data from Nextstrain. They then conducted phylogenetic analyses using IQ-TREE 2.3.6 and nucleotide pairwise distance (p-distance) analyses using MEGA11.0, comparing how the short region performed against the WGS-based classification system.

The phylogenetic analyses revealed that the primary lineages defined by the WGS-defined lineage nomenclature could be classified using the HVR2-G region, with bootstrap support over 70%. However, the nested lineages could not be distinguished using this short window, marking a clear boundary of its resolution.

The study also quantified how the historical genotyping scheme maps onto the new lineage system. Nineteen previous HVR2-G genotypes of HRSV subtype A were reduced to four lineages—A.1, A.2, A.3 and A.D—using a p-distance threshold greater than 0.102. For HRSV subtype B, 37 previous HVR2-G genotypes were reduced to five lineages—B.1, B.2, B.3, B.4 and B.D—using a p-distance threshold greater than 0.0591.

In its conclusion, the study verified that the HVR2-G sequencing window provides reliable assignment of major HRSV lineages and enables integration with historical surveillance datasets. The authors note that it has the potential to serve as a complement to the application of WGS for molecular virological surveillance of HRSV in China and globally, especially in resource-limited areas.

HRSV is among the major pathogens causing acute lower respiratory tract infections in infants, young children and older adults, making robust molecular surveillance an ongoing public health priority. The findings suggest that laboratories that cannot perform whole-genome sequencing can continue generating data compatible with the modern lineage nomenclature, while the accumulated decades of HVR2-G genotyping records can be reinterpreted within the current classification framework. The article was published as an open-access research paper on 27 October 2026 and is citable under a permanent DOI, with the authors noting that the early-release version is subject to further edits before the final Version of Record.

Subject of Research: Molecular epidemiology surveillance of HRSV using the HVR2-G gene region as a complement to whole-genome sequencing

Article Title: Using HVR2-G in molecular epidemiology surveillance of HRSV: a supplement for the application of WGS

Article References: Song, J., Zhu, Z., Wang, H., Li, H., Xia, B., Chen, J., Sun, L., Guo, Y., Liang, S., Tian, X., Chen, X., Zhao, L., Huang, F., Xie, Z., & Zhang, Y. (2026). Using HVR2-G in molecular epidemiology surveillance of HRSV: a supplement for the application of WGS. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14356-6

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14356-6

Keywords: HRSV, HVR2-G, whole-genome sequencing, molecular epidemiology, lineage classification, G gene, phylogenetics, p-distance, Nextstrain, GenBank, surveillance, BMC Infectious Diseases