National Influenza Centre (NIC), Royal Centre for Disease Control, Ministry of Health, Royal Government of Bhutan, Thimphu, Bhutan.
Influenza Other Respir Viruses. 2024 Oct;18(10):e70028. doi: 10.1111/irv.70028.
Influenza A viruses pose a significant public health threat globally and are characterized by rapid evolution of the hemagglutinin (HA) gene causing seasonal epidemics. The aim of this study was to investigate the evolutionary dynamics of A(H3N2) circulating in Bhutan during 2022 and 2023.
We analysed 166 whole-genome sequences of influenza A(H3N2) from Bhutan, obtained from the GISAID database. We employed a Bayesian Markov Chain Monte Carlo (MCMC) framework, with a curated global dataset of HA sequences from regions with significant migration links to Bhutan. Phylogenetic, temporal, and phylogeographic analyses were conducted to elucidate the evolutionary dynamics and spatial dissemination of the viruses.
Our phylogenetic analysis identified the circulation of influenza A(H3N2) Clade 3C.2a1b.2a.2 in Bhutan during 2022 and 2023, with viruses further classified into three subclades: 2a.3 (39/166), 2a.3a.1 (58/166) and 2a.3b (69/166). The TMRCA estimates suggest that these viral lineages originated approximately 1.93 years prior to their detection. Phylogeographic analysis indicates introductions from the United States in 2022 and Australia in 2023. The mean evolutionary rate across all gene segments was calculated to be 4.42 × 10 substitutions per site per year (95% HPD: 3.19 × 10 to 5.84 × 10), with evidence of purifying selection and limited genetic diversity. Furthermore, reassortment events were rare, with an estimated rate of 0.045 events per lineage per year.
Our findings show that primary forces shaping the local evolution of the influenza A(H3N2) in Bhutan are largely stochastic, with only sporadic instances of adaptive change, and thus underscore the importance of continuous surveillance to mitigate the impact of evolving strains.
甲型流感病毒在全球范围内构成重大公共卫生威胁，其特征是血凝素（HA）基因的快速进化，导致季节性流行。本研究旨在调查 2022 年和 2023 年在不丹流行的 A(H3N2)的进化动态。
我们分析了从 GISAID 数据库中获得的来自不丹的 166 株甲型流感 A(H3N2)的全基因组序列。我们采用贝叶斯马尔可夫链蒙特卡罗（MCMC）框架，结合具有与不丹有显著迁移联系的 HA 序列的全球精选数据集。进行系统发育、时间和系统地理学分析，以阐明病毒的进化动态和空间传播。
我们的系统发育分析鉴定了 2022 年和 2023 年在不丹流行的甲型流感 A(H3N2)属 3C.2a1b.2a.2 分支，病毒进一步分为三个亚分支：2a.3（39/166）、2a.3a.1（58/166）和 2a.3b（69/166）。TMRCA 估计表明，这些病毒谱系起源于检测前约 1.93 年。系统地理学分析表明，2022 年的病毒来源于美国，2023 年的病毒来源于澳大利亚。所有基因片段的平均进化率计算为每年每核苷酸 4.42×10 个取代（95% HPD：3.19×10 至 5.84×10），存在纯化选择和有限遗传多样性的证据。此外，重组事件很少，估计每年每个谱系发生 0.045 次重组事件。
我们的研究结果表明，塑造不丹甲型流感 A(H3N2)本地进化的主要力量主要是随机的，只有偶尔出现适应性变化，因此强调了持续监测以减轻不断进化的菌株的影响的重要性。
