Jo Wendy K, Anzolini Cassiano Murilo Henrique, de Oliveira-Filho Edmilson Ferreira, Brünink Sebastian, Yansanjav Adiya, Yihune Mesele, Koshkina Alyona I, Lukashev Alexander N, Lavrenchenko Leonid A, Lebedev Vladimir S, Olayemi Ayodeji, Bangura Umaru, Salas-Rojas Mónica, Aguilar-Setién Álvaro, Fichet-Calvet Elisabeth, Drexler Jan Felix
Institute of Virology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin 10117, Germany.
Mammalian Ecology Laboratory, Institute of Biology, Mongolian Academy of Sciences, Ulaanbaatar 13330, Mongolia.
Proc Natl Acad Sci U S A. 2024 Dec 17;121(51):e2413665121. doi: 10.1073/pnas.2413665121. Epub 2024 Dec 9.
Hepatitis E virus (HEV; family ) infections cause >40,000 human deaths annually. Zoonotic infections predominantly originate from ungulates and occasionally from rats, highlighting the zoonotic potential of rodent-associated hepeviruses. We conducted host genomic data mining and uncovered two genetically divergent rodent-associated hepeviruses, and two bat-associated hepeviruses genetically related to known bat-associated strains. We thus analyzed 2,565 liver specimens from 108 rodent and shrew species sampled from globally understudied regions and hosts in Africa, Asia, and Latin America during 2011-2018 for hepeviruses by RT-PCR. We detected 63 positive field samples (2.5%, 95% CI 1.9-3.1) from 14 animal species, including two coinfections with genetically divergent strains and significant variation (, < 0.001) in detection rates between study sites. Strain-specific qRT-PCR assays showed virus concentrations between 9.2 × 10 and 3.2 × 10 copies/g. We recovered 24 near-complete hepeviral genomes from rodents, shrews, and bats, all showing three partially overlapping open reading frames (ORFs), some including putative late domains that may be associated with quasi-envelopment. Rodent-derived hepeviruses grouped into five clades clustering in basal sister relationship to human- (31 to 84% distance in translated ORF1-3) and rat-associated HEV. Parsimony-based analyses and cophylogenetic reconciliations revealed that rodents were predominant sources of hepeviral cross-order host shifts. Bayesian ancestral state reconstructions substantiated a direct origin of human-associated HEV in ungulates such as swine and camelids (posterior probability 0.8), whereas the nonrecent evolutionary origins of human- and ungulate-associated HEV were projected to rodent hosts (posterior probability > 0.9). Our results elucidate the genealogy of human HEV and warrant increased surveillance and experimental risk assessments for rodent-associated hepeviruses.
戊型肝炎病毒（HEV；科）感染每年导致超过40000人死亡。人畜共患感染主要源于有蹄类动物，偶尔也源于大鼠，这突出了啮齿动物相关肝炎病毒的人畜共患潜力。我们进行了宿主基因组数据挖掘，发现了两种基因不同的啮齿动物相关肝炎病毒，以及两种与已知蝙蝠相关毒株有基因关联的蝙蝠相关肝炎病毒。因此，我们在2011年至2018年期间，通过逆转录聚合酶链反应（RT-PCR）分析了从非洲、亚洲和拉丁美洲全球研究不足的地区和宿主中采集的108种啮齿动物和鼩鼱物种的2565份肝脏标本，以检测肝炎病毒。我们从14种动物物种中检测到63份阳性野外样本（2.5%，95%置信区间1.9 - 3.1），包括两例基因不同毒株的共感染，且研究地点之间的检测率存在显著差异（，< 0.001）。菌株特异性定量逆转录聚合酶链反应（qRT-PCR）检测显示病毒浓度在9.2×10至3.2×10拷贝/克之间。我们从啮齿动物、鼩鼱和蝙蝠中获得了24个近乎完整的肝炎病毒基因组，所有基因组均显示出三个部分重叠的开放阅读框（ORF），有些还包括可能与准包膜相关的假定晚期结构域。源自啮齿动物的肝炎病毒分为五个进化枝，与人类（翻译后的ORF1 - 3中距离为31%至84%）和大鼠相关的戊型肝炎病毒聚为基部姐妹关系。基于简约法的分析和共系统发育和解表明，啮齿动物是肝炎病毒跨目宿主转移的主要来源。贝叶斯祖先状态重建证实，人类相关戊型肝炎病毒直接起源于猪和骆驼科等有蹄类动物（后验概率0.8），而人类和有蹄类动物相关戊型肝炎病毒的非近期进化起源则推测源于啮齿动物宿主（后验概率> 0.9）。我们的研究结果阐明了人类戊型肝炎病毒的谱系，并为加强对啮齿动物相关肝炎病毒的监测和实验风险评估提供了依据。
