Kim Dong Hyun, Choi Yu-Min, Jang Junghwa, 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.
Front Microbiol. 2023 Mar 9;14:1137084. doi: 10.3389/fmicb.2023.1137084. eCollection 2023.
Hepatitis B Virus (HBV) genotypes reflect geographic, ethical or clinical traits and are currently divided into 10 genotypes (A-J). Of these, genotype C is mainly distributed in Asia, is the largest group and comprises more than seven subgenotypes (C1-C7). Subgenotype C2 is divided into three phylogenetically distinct clades, C2(1), C2(2), and C2(3), and is responsible for most genotype C infections in three East Asian nations, including China, Japan, and South Korea, which are major HBV endemic areas. However, despite the significance of subgenotype C2 with regard to clinical or epidemiologic aspects, its global distribution and molecular characteristics remain largely unknown. Here, we analyze the global prevalence and molecular characteristics between 3 clades within subgenotype C2 using 1,315 full genome sequences of HBV genotype C retrieved from public databases. Our data show that almost all HBV strains from South Korean patients infected with genotype C belong to clade C2(3) within subgenotype C2 [96.3%] but that HBV strains from Chinese or Japanese patients belong to diverse subgenotypes or clades within genotype C, suggesting clonal expansion of a specific HBV type, C2(3), among the Korean population. Our genome sequence analysis indicated a total of 21 signature sequences specific to the respective clades C2(1), C2(2), and C2(3). Of note, two types of four nonsynonymous C2(3) signature sequences, sV184A in HBsAg and xT36P in the X region, were detected in 78.9 and 82.9% of HBV C2(3) strains, respectively. In particular, HBV strains C2(3) versus C2(1) and C2(2) show a higher frequency of reverse transcriptase mutations related to nucleot(s)ide analog (NA) resistance, including rtM204I and rtL180M, suggesting an increased possibility of C2(3) infection in those with NA treatment failure. In conclusion, our data show that HBV subgenotype C2(3) is extremely prevalent in Korean patients with chronic HBV infection, which is distinct from two other East Asian nations, China and Japan, where diverse subgenotypes or clades within genotype C coexist. This epidemiologic trait might affect distinct virological and clinical traits in chronic HBV patients in Korea, where exclusively C2(3) infection is predominant.
乙型肝炎病毒（HBV）基因型反映了地域、种族或临床特征，目前分为10种基因型（A - J）。其中，C基因型主要分布在亚洲，是最大的组，包含7种以上的亚基因型（C1 - C7）。亚基因型C2分为三个系统发育上不同的分支，C2(1)、C2(2)和C2(3)，在包括中国、日本和韩国这三个主要HBV流行地区的三个东亚国家中，C2亚基因型导致了大多数C基因型感染。然而，尽管C2亚基因型在临床或流行病学方面具有重要意义，但其全球分布和分子特征仍 largely未知。在此，我们使用从公共数据库中检索到的1315个HBV C基因型全基因组序列，分析了C2亚基因型内3个分支之间的全球流行情况和分子特征。我们的数据显示，几乎所有韩国感染C基因型的患者的HBV毒株都属于C2亚基因型内的C2(3)分支[96.3%]，但中国或日本患者的HBV毒株属于C基因型内不同的亚基因型或分支，这表明特定的HBV类型C2(3)在韩国人群中发生了克隆扩增。我们的基因组序列分析表明，共有21个分别特定于C2(1)、C2(2)和C2(3)分支的特征序列。值得注意的是，在78.9%和82.9%的HBV C2(3)毒株中分别检测到了两种类型的四个非同义C2(3)特征序列，即HBsAg中的sV184A和X区域中的xT36P。特别是，与C2(1)和C2(2)相比，C2(3)分支的HBV毒株显示出与核苷（酸）类似物（NA）耐药相关的逆转录酶突变频率更高，包括rtM204I和rtL180M，这表明在接受NA治疗失败的患者中C2(3)感染的可能性增加。总之，我们的数据表明，HBV C2(3)亚基因型在韩国慢性HBV感染患者中极为普遍，这与另外两个东亚国家中国和日本不同，在中国和日本，C基因型内不同的亚基因型或分支共存。这种流行病学特征可能会影响韩国慢性HBV患者独特的病毒学和临床特征，在韩国，仅C2(3)感染占主导地位。
