Liver and Bile

Hepatology. 2023;77(5):1722–34

Ying D, He Q, Tian W, Chen Y, Zhang X, Wang S, Liu C, Chen Z, Liu Y, Fu L, Yan L, Wang L, Tang Z, Wang L, Zheng Z, Xia N

Urine is a viral antigen reservoir in hepatitis E virus infection

Background and aims: Hepatitis E virus (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. The authors 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. Antigen in urine was analyzed by biochemical and proteomic approaches. The origin of urinary Ag and Ag kinetics during HEV infection was inves-tigated in mouse and rabbit models, respectively. It was 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 intravenously injected with pORF2. Antigen in urine originated from the secreted form of pORF2 (ORF2S) 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 high-er 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: These findings demonstrated the origin and diagnostic value of urine antigen and provided insights into the disposal of exogenous protein of pathogens by the host kidney.

Z. Tang or Z. Zheng or N. Xia, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, School of Life Sciences, Xiamen University, Xiamen, China,
E-Mail: zimin-tang@163.com or E-Mail: zhengzizheng@xmu.edu.cn or E-Mail: nsxia@xmu.edu.cn

or

L. Wang, Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China,
E-Mail: lin_wang@pku.edu.cn

DOI: 10.1002/hep.32745

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