I. Department of Medicine, Gastroenterology and Hepatology, with the Sections Infectious Diseases and Tropical Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; German Center for Infection Research (DZIF), Hamburg-Lübeck-Borstel-Riems and Heidelberg Partner sites, Germany.
Ruhr University Bochum, Faculty of Medicine, Department of Molecular and Medical Virology, Bochum, Germany.
J Hepatol. 2021 Jul;75(1):55-63. doi: 10.1016/j.jhep.2020.12.030. Epub 2021 Jan 20.
BACKGROUND & AIMS: Hepatitis E virus (HEV) infections are prevalent worldwide. Various viruses have been detected in the ejaculate and can outlast the duration of viremia, indicating replication beyond the blood-testis barrier. HEV replication in diverse organs, however, is still widely misunderstood. We aimed to determine the occurrence, features and morphology of HEV in the ejaculate.
The presence of HEV in testis was assessed in 12 experimentally HEV-genotype 3-infected pigs. We further tested ejaculate, urine, stool and blood from 3 chronically HEV genotype 3-infected patients and 6 immunocompetent patients with acute HEV infection by HEV-PCR. Morphology and genomic characterization of HEV particles from various human compartments were determined by HEV-PCR, density gradient measurement, immune-electron microscopy and genomic sequencing.
In 2 of the 3 chronically HEV-infected patients, we observed HEV-RNA (genotype 3c) in seminal plasma and semen with viral loads >2 logs higher than in the serum. Genomic sequencing showed significant differences between viral strains in the ejaculate compared to stool. Under ribavirin-treatment, HEV shedding in the ejaculate continued for >9 months following the end of viremia. Density gradient measurement and immune-electron microscopy characterized (enveloped) HEV particles in the ejaculate as intact.
The male reproductive system was shown to be a niche of HEV persistence in chronic HEV infection. Surprisingly, sequence analysis revealed distinct genetic HEV variants in the stool and serum, originating from the liver, compared to variants in the ejaculate originating from the male reproductive system. Enveloped HEV particles in the ejaculate did not morphologically differ from serum-derived HEV particles.
Enveloped hepatitis E virus particles could be identified by PCR and electron microscopy in the ejaculate of immunosuppressed chronically infected patients, but not in immunocompetent experimentally infected pigs or in patients with acute self-limiting hepatitis E.
戊型肝炎病毒（HEV）感染在全球范围内普遍存在。已在精液中检测到多种病毒，且这些病毒的存在时间超过了病毒血症的持续时间，表明其在血睾屏障之外进行复制。然而，HEV 在多种器官中的复制仍存在广泛的误解。本研究旨在确定 HEV 在精液中的存在、特征和形态。
我们在 12 只经实验性 HEV 基因型 3 感染的猪中评估了睾丸中 HEV 的存在情况。我们还通过 HEV-PCR 检测了 3 例慢性 HEV 基因型 3 感染患者和 6 例免疫功能正常的急性 HEV 感染患者的精液、尿液、粪便和血液。通过 HEV-PCR、密度梯度测量、免疫电子显微镜和基因组测序，确定了来自不同人体部位的 HEV 颗粒的形态和基因组特征。
在 3 例慢性 HEV 感染患者中的 2 例中，我们观察到精液和精子中的 HEV-RNA（基因型 3c），其病毒载量比血清高 2 个对数级以上。基因组测序显示，与粪便相比，精液中的病毒株存在明显差异。在接受利巴韦林治疗期间，病毒血症结束后，精液中的 HEV 脱落持续了>9 个月。密度梯度测量和免疫电子显微镜将精液中的（包膜）HEV 颗粒鉴定为完整颗粒。
本研究表明，男性生殖系统是慢性 HEV 感染中 HEV 持续存在的场所。令人惊讶的是，序列分析显示，粪便和血清中的肝脏来源的 HEV 变体与来自男性生殖系统的精液中的变体在遗传上存在明显差异。来自精液的包膜 HEV 颗粒在形态上与来自血清的 HEV 颗粒没有区别。
免疫抑制的慢性感染患者的精液中可通过 PCR 和电子显微镜鉴定出包膜的 HEV 颗粒，但免疫功能正常的实验性感染猪或急性自限性肝炎 E 患者的精液中则无法鉴定。
