Urine is a viral antigen reservoir in hepatitis E virus infection
Urine is a viral antigen reservoir in hepatitis E virus infection
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尿液是戊型肝炎病毒感染的病毒抗原库
DOI：
10.1002/hep.32745
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发表时间：
2022-10-13
期刊：
影响因子：
13.5
通讯作者：
Xia, Ningshao
中科院分区：
文献类型：
--
作者：
Ying, Dong;He, Qiyu;Xia, Ningshao
背景与目的血清中HEV ORF2抗原（Ag）已成为诊断当前HEV感染的一种工具。特别是，HEV Ag的尿脱落已经获得越来越多的关注。我们的目的是揭示的来源，抗原性，诊断性能，并在戊型肝炎病毒感染的尿液中的诊断意义。方法和结果分析了急性和慢性戊型肝炎病毒感染患者的临床血清和尿液样本的抗原水平。用生化和蛋白质组学方法分析尿中的Ag。在小鼠和家兔模型上，分别研究了戊型肝炎病毒（HEV）感染期间尿Ag的来源和Ag动力学。发现尿中Ag含量及诊断敏感性均高于血清。尿中的抗原蛋白是跨越氨基酸453 - 606的E2s样二聚体。在静脉注射pORF 2的小鼠中，pORF 2从血清进入尿液。尿中Ag来源于戊型肝炎患者血清中大量存在的pORF2（S）的分泌型。肾细胞特异性地摄取HEV抗原，并将其排入尿液，尿液中的抗原浓度可达10倍以上，因此尿抗原的诊断敏感性高于血清抗原。此外，在兔模型中，尿液中的Ag出现早6天，持续时间长于病毒血症和抗原血症，并与粪便RNA显示出良好的一致性。结论本研究揭示了尿Ag的来源及诊断价值，为了解宿主肾对病原体外源性蛋白的处理提供了依据。
Background and Aims HEV ORF2 antigen (Ag) in serum has become a tool for diagnosing current HEV infection. Particularly, urinary shedding of HEV Ag has been gaining increasing interest. We aim to uncover the origin, antigenicity, diagnostic performance, and diagnostic significance of Ag in urine in HEV infection. Approach and Results Clinical serum and urine samples from patients with acute and chronic HEV infection were analyzed for their Ag levels. Ag in urine was analyzed by biochemical and proteomic approaches. The origin of urinary Ag and Ag kinetics during HEV infection was investigated in mouse and rabbit models, respectively. We found that both the Ag level and diagnostic sensitivity in urine were higher than in serum. Antigenic protein in urine was an E2s-like dimer spanning amino acids 453-606. pORF2 entered urine from serum in mice i.v. injected with pORF2. Ag in urine originated from the secreted form of pORF2 (ORF2(S)) that abundantly existed in hepatitis E patients' serum. HEV Ag was specifically taken up by renal cells and was disposed into urine, during which the level of Ag was concentrated >10-fold, resulting in the higher diagnosing sensitivity of urine Ag than serum Ag. Moreover, Ag in urine appeared 6 days earlier, lasted longer than viremia and antigenemia, and showed good concordance with fecal RNA in a rabbit model. Conclusions Our findings demonstrated the origin and diagnostic value of urine Ag and provided insights into the disposal of exogenous protein of pathogens by the host kidney.