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Volume 41 Issue 5
October 2026
    Citation: Jingqi Yang, Yuhua Liao, Luyao Qin, Haoyang Wang, Yun Ma, Ye Tong, Fei Deng, Liguo Zhu, Hang-Yu Zhou, Aiping Wu. Recurrent intrahost G-gene haplotype structures suggest potential co-transmission in RSV-A .VIROLOGICA SINICA, 2026, 41(5) : 1054-1065.  http://dx.doi.org/10.1016/j.virs.2026.10.003
    shu

    Recurrent intrahost G-gene haplotype structures suggest potential co-transmission in RSV-A

    • a. State Key Laboratory of Common Mechanism Research for Major Diseases, Suzhou Institute of Systems Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Suzhou, 215123, China;

    • b. Department of Acute Infectious Disease Control and Prevention, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, 210009, China

    • Respiratory syncytial virus (RSV) is a leading cause of infant hospitalization worldwide. Its molecular epidemiology rests on consensus G-gene sequences, which capture only the dominant virus in each infection. Deep sequencing reveals far more variation inside each host. Linking those variants to one another gives a finer view of transmission. Here we reconstructed G-gene haplotypes from two independent RSV-A deep-sequencing datasets (Australia, n = 37; United States, n = 72). We phased variants using read-level linkage, then placed each haplotype on a global phylogeny. More than 90% of samples carry multiple haplotypes, which often sit on distinct phylogenetic branches. One cross-branch pair dominates each dataset: C4+C6 in 23 of 37 Australian samples (62%), and C18 + C21 in 26 of 72 US samples (36%). Both pairs recur far more often than month- and region-matched permutations predict (both P = 5.0 × 10-5). Mutation-probability calculations suggest that recurrent within-host de novo mutation is unlikely to fully account for these patterns, particularly for the five linked sites in C4+C6 (probability ≤5.36 × 10-15). Repeated joint introduction of pre-existing haplotypes offers a simpler explanation, and transmission-chain sampling can now test it directly. All branch-defining sites mapped to G-HVR2. In the examined global consensus G-gene set, dominant-branch states appeared, while minor-branch combinations were not detected under our criteria. Haplotype-resolved analysis thus turns sub-consensus diversity into linked, interpretable epidemiological signal.
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      Recurrent intrahost G-gene haplotype structures suggest potential co-transmission in RSV-A

        Corresponding author: Liguo Zhu, zhuliguo2002@163.com
        Corresponding author: Hang-Yu Zhou, zhy@ism.cams.cn
        Corresponding author: Aiping Wu, wap@ism.cams.cn
      • a. State Key Laboratory of Common Mechanism Research for Major Diseases, Suzhou Institute of Systems Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Suzhou, 215123, China;
      • b. Department of Acute Infectious Disease Control and Prevention, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, 210009, China
      • Received Date: 15 July 2026
      • Accepted Date: 03 October 2026

      Abstract: Respiratory syncytial virus (RSV) is a leading cause of infant hospitalization worldwide. Its molecular epidemiology rests on consensus G-gene sequences, which capture only the dominant virus in each infection. Deep sequencing reveals far more variation inside each host. Linking those variants to one another gives a finer view of transmission. Here we reconstructed G-gene haplotypes from two independent RSV-A deep-sequencing datasets (Australia, n = 37; United States, n = 72). We phased variants using read-level linkage, then placed each haplotype on a global phylogeny. More than 90% of samples carry multiple haplotypes, which often sit on distinct phylogenetic branches. One cross-branch pair dominates each dataset: C4+C6 in 23 of 37 Australian samples (62%), and C18 + C21 in 26 of 72 US samples (36%). Both pairs recur far more often than month- and region-matched permutations predict (both P = 5.0 × 10-5). Mutation-probability calculations suggest that recurrent within-host de novo mutation is unlikely to fully account for these patterns, particularly for the five linked sites in C4+C6 (probability ≤5.36 × 10-15). Repeated joint introduction of pre-existing haplotypes offers a simpler explanation, and transmission-chain sampling can now test it directly. All branch-defining sites mapped to G-HVR2. In the examined global consensus G-gene set, dominant-branch states appeared, while minor-branch combinations were not detected under our criteria. Haplotype-resolved analysis thus turns sub-consensus diversity into linked, interpretable epidemiological signal.

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