Distinct phylogeographic distributions and frequencies of precore and basal core promoter mutations between HBV subgenotype C1 rt269L and rt269I types

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.