戊型肝炎病毒(HEV)可引起自限性急性和慢性肝炎感染,特别是在免疫受损的个体中。在发展中国家,HEV主要通过饮用受污染的水传播,尽管人畜共患传播在发达国家的感染途径中占主导地位,包括日本。猪是HEV感染的重要宿主。野猪,与家猪有相同的属和种,也是HEV水库。在我们对日本野猪种群中HEV感染的全国性研究中,基因型6(HEV-6)菌株,wbJHG_23,于2023年在兵库县被隔离。基因组长度为7244个核苷酸,不包括聚(A)道。wbJHG_23菌株在其整个基因组中表现出最高的核苷酸同一性,具有两个先前报道的HEV-6菌株(80.3-80.9%)。相反,与HEV-1-5、HEV-7和HEV-8菌株的相似性较低(73.3-78.1%),表明,虽然密切相关,wbJHG_23菌株与报道的HEV-6菌株显着不同,可能代表一种新的亚型。wbJHG_23株成功感染人源癌细胞系,PLC/PRF/5和A5491-1H8电池,这表明HEV-6具有人畜共患感染的潜力。使用反向遗传学系统构建了感染性cDNA克隆,并建立了支持HEV-6菌株有效繁殖的细胞培养系统,为进一步研究这种基因型提供了重要的工具。使用这个细胞培养系统,我们评估了wbJHG_23菌株对利巴韦林治疗的敏感性。它对这种治疗的良好反应表明它可用于治疗由HEV-6引起的人类感染。
Hepatitis E virus (HEV) can cause self-limiting acute and chronic hepatitis infections, particularly in immunocompromised individuals. In developing countries, HEV is mainly transmitted via drinking contaminated water, whereas zoonotic transmission dominates the route of infection in developed countries, including Japan. Pigs are an important reservoir for HEV infection. Wild boars, which share the same genus and species as domestic pigs, are also an HEV reservoir. During our nationwide study of HEV infection in wild boar populations in Japan, a genotype 6 (HEV-6) strain, wbJHG_23, was isolated in Hyogo Prefecture in 2023. The genomic length was 7244 nucleotides, excluding the poly(A) tract. The wbJHG_23 strain exhibited the highest nucleotide identity throughout its genome with two previously reported HEV-6 strains (80.3-80.9%). Conversely, it displayed lower similarity (73.3-78.1%) with the HEV-1-5, HEV-7, and HEV-8 strains, indicating that, although closely related, the wbJHG_23 strain differs significantly from the reported HEV-6 strains and might represent a novel subtype. The wbJHG_23 strain successfully infected the human-derived cancer cell lines, PLC/PRF/5 and A549 1-1H8 cells, suggesting that HEV-6 has the potential for zoonotic infection. An infectious cDNA clone was constructed using a reverse genetics system, and a cell culture system supporting the efficient propagation of the HEV-6 strain was established, providing important tools for further studies on this genotype. Using this cell culture system, we evaluated the sensitivity of the wbJHG_23 strain to ribavirin treatment. Its good response to this treatment suggested that it could be used to treat human infections caused by HEV-6.