Classification of hepatitis A virus in clades based on VP1/2A region allows higher geographic and temporal resolution than conventional genotyping: a global sequences analysis

Infections caused by the Hepatitis A virus (HAV) occur worldwide. Molecular epidemiology is crucial to understanding the transmission dynamics; however, the current genotype assignment fails to provide useful epidemiologic information. We classified HAV sequences available in GenBank based on 460 bp of the VP1/2A region in clades. Additionally, we associated the site of isolation of the strains with the country’s HAV endemicity. We analyzed 1369 sequences available in GenBank up to December 2023 which fulfilled inclusion criteria for our study. The collection date ranged from 1957 to 2023, and genotypes IA (<i>n</i> = 986) and IB (<i>n</i> = 290) comprised the majority of sequences. Sequences were assigned to 70 different clades; sequences from most clades (<i>n</i> = 36) were detected in one country or a few countries within a single continent, while sequences of only 9 clades were detected in more than two continents. Countries with lower HAV endemicity showed higher diversity of clades compared with countries with higher HAV endemicity. In addition, multinational HAV outbreaks were associated with specific clades. In conclusion, characterization of HAV strains below the genotype level should be helpful to analyze transmission patterns within and between countries.

甲型肝炎病毒（Hepatitis A virus, HAV）引发的感染在全球范围内均有分布。分子流行病学对于阐明该病毒的传播动态至关重要，但当前的基因型分型方案无法提供有效的流行病学信息。本研究基于VP1/2A基因区域460 bp的序列片段，将GenBank数据库中收录的甲肝病毒序列划分为进化支，同时将毒株的分离位点与所在国的甲肝流行程度进行关联分析。本研究共分析了截至2023年12月收录于GenBank、符合纳入标准的1369条甲肝病毒序列，所有序列的采集时间跨度为1957年至2023年，其中基因型IA（n=986）与IB（n=290）占总序列数的绝大多数。这些序列被划分为70个不同的进化支：其中36个进化支的序列仅在单个大陆内的一个或少数几个国家中被检出，仅9个进化支的序列在两个及以上大陆中被检测到。与甲肝高流行国家相比，低流行国家的甲肝病毒进化支多样性更高。此外，跨国甲型肝炎暴发事件与特定进化支存在显著关联。综上，在基因型水平以下对甲肝病毒毒株进行分型鉴定，将有助于解析国家内部及国家间的病毒传播模式。