Kim Dong Hyun, Choi Yu-Min, Jang Junghwa, Kim Ziyun, Kim Bum-Joon
Department of Microbiology and Immunology, College of Medicine, Seoul National University, Seoul, Republic of Korea.
Department of Biomedical Sciences, College of Medicine, Seoul National University, Seoul, Republic of Korea.
Sci Rep. 2025 Mar 18;15(1):9315. doi: 10.1038/s41598-025-94286-6.
Hepatitis B virus (HBV) genotype C exhibits two distinct polymorphisms in its viral polymerase: rt269I and rt269L. Recently, we reported that there are distinct virological and clinical profiles between chronic patients with subgenotype C2 with the rt269I polymorphism and those with the rt269L polymorphism, with the latter being more closely related to liver disease severity. This study explored the phylogenetic and geographic distributions, as well as the mutation frequencies, of precore (T1858C/G1896A) and basal core promoter (BCP) (A1762T/G1764A) mutations between these two types within the HBV subgenotype C1. Analysis of 408 HBV/C1 full-genome sequences from GenBank revealed clear phylogenetic separation between rt269L and rt269I in subgenotype C1. Geographically, rt269I strains within subgenotype C1 are predominant in Southwest Asia (e.g., Thailand and Bangladesh), whereas rt269L strains are more common in East Asia and Southeast Asia (e.g., Vietnam, China, and Hong Kong). Notably, compared with rt269L in subgenotype C2, rt269I presented higher frequencies of the C1858 and BCP mutations but lower frequencies of the G1896A mutation. These findings suggest significantly distinct phylogeographic and mutational characteristics of the rt269L and rt269I types of subgenotype C1, impacting clinical outcomes and evolutionary trajectories.
乙型肝炎病毒(HBV)C基因型在其病毒聚合酶中表现出两种不同的多态性:rt269I和rt269L。最近,我们报道了具有rt269I多态性的C2亚基因型慢性患者与具有rt269L多态性的慢性患者之间存在明显的病毒学和临床特征,后者与肝病严重程度的关系更为密切。本研究探讨了HBV C1亚基因型中这两种类型之间前核心(T1858C/G1896A)和核心启动子(BCP)(A1762T/G1764A)突变的系统发育和地理分布以及突变频率。对来自GenBank的408条HBV/C1全基因组序列的分析显示,C1亚基因型中rt269L和rt269I之间存在明显的系统发育分离。在地理上,C1亚基因型中的rt269I毒株在西南亚(如泰国和孟加拉国)占主导地位,而rt269L毒株在东亚和东南亚(如越南、中国和香港)更为常见。值得注意的是,与C2亚基因型中的rt269L相比,rt269I的C1858和BCP突变频率较高,但G1896A突变频率较低。这些发现表明,C1亚基因型的rt269L和rt269I类型具有明显不同的系统地理和突变特征,影响临床结局和进化轨迹。