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A novel hepatitis B virus species discovered in capuchin monkeys sheds new light on the evolution of primate hepadnaviruses
Journal of Hepatology ( IF 25.7 ) Pub Date : 2018-06-01 , DOI: 10.1016/j.jhep.2018.01.029
Breno Frederico de Carvalho Dominguez Souza , Alexander König , Andrea Rasche , Ianei de Oliveira Carneiro , Nora Stephan , Victor Max Corman , Pia Luise Roppert , Nora Goldmann , Ramona Kepper , Simon Franz Müller , Christof Völker , Alex Junior Souza de Souza , Michele Soares Gomes-Gouvêa , Andrés Moreira-Soto , Andreas Stöcker , Michael Nassal , Carlos Roberto Franke , João Renato Rebello Pinho , Manoel do Carmo Pereira Soares , Joachim Geyer , Philippe Lemey , Christian Drosten , Eduardo Martins Netto , Dieter Glebe , Jan Felix Drexler

BACKGROUND & AIMS All known hepatitis B virus (HBV) genotypes occur in humans and hominoid Old World non-human primates (NHPs). The divergent woolly monkey HBV (WMHBV) forms another orthohepadnavirus species. The evolutionary origins of HBV are unclear. METHODS We analysed sera from 124 Brazilian monkeys collected during 2012-2016 for hepadnaviruses using molecular and serological tools, and conducted evolutionary analyses. RESULTS We identified a novel orthohepadnavirus species in capuchin monkeys (capuchin monkey hepatitis B virus [CMHBV]). We found CMHBV-specific antibodies in five animals and high CMHBV concentrations in one animal. Non-inflammatory, probably chronic infection was consistent with an intact preCore domain, low genetic variability, core deletions in deep sequencing, and no elevated liver enzymes. Cross-reactivity of antisera against surface antigens suggested antigenic relatedness of HBV, CMHBV, and WMHBV. Infection-determining CMHBV surface peptides bound to the human HBV receptor (human sodium taurocholate co-transporting polypeptide), but preferentially interacted with the capuchin monkey receptor homologue. CMHBV and WMHBV pseudotypes infected human hepatoma cells via the human sodium taurocholate co-transporting polypeptide, and were poorly neutralised by HBV vaccine-derived antibodies, suggesting that cross-species infections may be possible. Ancestral state reconstructions and sequence distance comparisons associated HBV with humans, whereas primate hepadnaviruses as a whole were projected to NHP ancestors. Co-phylogenetic analyses yielded evidence for co-speciation of hepadnaviruses and New World NHP. Bayesian hypothesis testing yielded strong support for an association of the HBV stem lineage with hominoid ancestors. Neither CMHBV nor WMHBV was likely the ancestor of the divergent human HBV genotypes F/H found in American natives. CONCLUSIONS Our data suggest ancestral co-speciation of hepadnaviruses and NHP, and an Old World origin of the divergent HBV genotypes F/H. The identification of a novel primate hepadnavirus offers new perspectives for urgently needed animal models of chronic hepatitis B. LAY SUMMARY The origins of HBV are unclear. The new orthohepadnavirus species from Brazilian capuchin monkeys resembled HBV in elicited infection patterns and could infect human liver cells using the same receptor as HBV. Evolutionary analyses suggested that primate HBV-related viruses might have emerged in African ancestors of New World monkeys millions of years ago. HBV was associated with hominoid primates, including humans and apes, suggesting evolutionary origins of HBV before the formation of modern humans. HBV genotypes found in American natives were divergent from those found in American monkeys, and likely introduced along prehistoric human migration. Our results elucidate the evolutionary origins and dispersal of primate HBV, identify a new orthohepadnavirus reservoir, and enable new perspectives for animal models of hepatitis B.

中文翻译:

在卷尾猴中发现的一种新型乙型肝炎病毒为灵长类肝炎病毒的进化提供了新的线索

背景和目的 所有已知的乙型肝炎病毒 (HBV) 基因型都发生在人类和人科旧大陆非人类灵长类动物 (NHP) 中。发散的毛猴 HBV (WMHBV) 形成另一种正肝炎病毒物种。HBV 的进化起源尚不清楚。方法我们使用分子和血清学工具分析了 2012-2016 年收集的 124 只巴西猴的血清中的肝炎病毒,并进行了进化分析。结果 我们在卷尾猴(卷尾猴乙型肝炎病毒 [CMHBV])中鉴定了一种新的正肝炎病毒种类。我们在五只动物中发现了 CMHBV 特异性抗体,在一只动物中发现了高 CMHBV 浓度。非炎症性、可能是慢性感染与完整的 preCore 域、低遗传变异性、深度测序中的核心缺失以及肝酶升高一致。抗血清对表面抗原的交叉反应表明 HBV、CMHBV 和 WMHBV 的抗原相关性。感染决定 CMHBV 表面肽与人 HBV 受体(人牛磺胆酸钠共转运多肽)结合,但优先与卷尾猴受体同源物相互作用。CMHBV 和 WMHBV 假型通过人牛磺胆酸钠共转运多肽感染人肝癌细胞,并且被 HBV 疫苗衍生的抗体弱中和,表明可能存在跨物种感染。祖先状态重建和序列距离比较将 HBV 与人类相关联,而灵长类肝炎病毒作为一个整体被预测到 NHP 祖先。共系统发育分析为嗜肝DNA 病毒和新世界 NHP 的共同物种形成提供了证据。贝叶斯假设检验为 HBV 干谱系与人类祖先的关联提供了强有力的支持。CMHBV 和 WMHBV 都不可能是在美国本土发现的不同人类 HBV 基因型 F/H 的祖先。结论 我们的数据表明肝炎病毒和 NHP 的祖先共同物种形成,以及不同 HBV 基因型 F/H 的旧世界起源。新型灵长类肝炎病毒的鉴定为急需的慢性乙型肝炎动物模型提供了新的视角。 概述 HBV 的起源尚不清楚。来自巴西卷尾猴的新正肝炎病毒物种在引发的感染模式上类似于 HBV,并且可以使用与 HBV 相同的受体感染人类肝细胞。进化分析表明,灵长类 HBV 相关病毒可能在数百万年前出现在新世界猴的非洲祖先中。HBV 与人科灵长类动物(包括人类和猿)有关,这表明 HBV 在现代人类形成之前的进化起源。在美国本土发现的 HBV 基因型与在美国猴子身上发现的不同,很可能是在史前人类迁徙过程中引入的。我们的结果阐明了灵长类动物 HBV 的进化起源和传播,确定了一个新的正肝炎病毒库,并为乙型肝炎动物模型提供了新的视角。在美国本土发现的 HBV 基因型与在美国猴子身上发现的不同,很可能是在史前人类迁徙过程中引入的。我们的结果阐明了灵长类动物 HBV 的进化起源和传播,确定了一个新的正肝炎病毒库,并为乙型肝炎动物模型提供了新的视角。在美国本土发现的 HBV 基因型与在美国猴子身上发现的不同,很可能是在史前人类迁徙过程中引入的。我们的结果阐明了灵长类动物 HBV 的进化起源和传播,确定了一个新的正肝炎病毒库,并为乙型肝炎动物模型提供了新的视角。
更新日期:2018-06-01
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