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Hepatitis E virus (HEV) open reading frame 2 antigen kinetics in human-liver chimeric mice and its impact on HEV diagnosis

(2019) JOURNAL OF INFECTIOUS DISEASES. 220(5). p.811-819
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Abstract
Background. Hepatitis E virus infection (HEV) is an emerging problem in developed countries. Diagnosis of HEV infection is based on the detection of HEV-specific antibodies, viral RNA, and/or antigen (Ag). Humanized mice were previously reported as a model for the study of HEV infection, but published data were focused on the quantification of viral RNA. However, the kinetics of HEV Ag expression during infection remains poorly understood. Methods. Plasma specimens and suspensions of fecal specimens from HEV-infected and ribavirin-treated humanized mice were analyzed using HEV antigen-specific enzyme-linked immunosorbent assay, reverse transcription-quantitative polymerase chain reaction analysis, density gradient analysis, and Western blotting. Result. Open reading frame 2 (ORF2) Ag was detected in both plasma and stool from HEV-infected mice, and levels increased over time. Contrary to HEV RNA, ORF2 Ag levels were higher in mouse plasma than in stool. Interestingly, ORF2 was detected in plasma from mice that tested negative for HEV RNA in plasma but positive for HEV RNA in stool and was detected after viral clearance in mice that were treated with ribavirin. Plasma density gradient analysis revealed the presence of the noninfectious glycosylated form of ORF2. Conclusion: ORF2 Ag can be used as a marker of active HEV infection and for assessment of the effect of antiviral therapy, especially when fecal samples are not available or molecular diagnostic tests are not accessible.
Keywords
HEV Ag, humanized mice, ORF2, diagnosis, ribavirin therapy, INFECTION, GENOTYPE, RIBAVIRIN, CAMELS, MARKER, MODEL

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MLA
Ibrahim Mahmoud Sayed, Ibrahim, et al. “Hepatitis E Virus (HEV) Open Reading Frame 2 Antigen Kinetics in Human-Liver Chimeric Mice and Its Impact on HEV Diagnosis.” JOURNAL OF INFECTIOUS DISEASES, vol. 220, no. 5, 2019, pp. 811–19, doi:10.1093/infdis/jiz171.
APA
Ibrahim Mahmoud Sayed, I., Verhoye, L., Montpellier, C., Abravanel, F., Izopet, J., Cocquerel, L., & Meuleman, P. (2019). Hepatitis E virus (HEV) open reading frame 2 antigen kinetics in human-liver chimeric mice and its impact on HEV diagnosis. JOURNAL OF INFECTIOUS DISEASES, 220(5), 811–819. https://doi.org/10.1093/infdis/jiz171
Chicago author-date
Ibrahim Mahmoud Sayed, Ibrahim, Lieven Verhoye, Claire Montpellier, Florence Abravanel, Jacques Izopet, Laurence Cocquerel, and Philip Meuleman. 2019. “Hepatitis E Virus (HEV) Open Reading Frame 2 Antigen Kinetics in Human-Liver Chimeric Mice and Its Impact on HEV Diagnosis.” JOURNAL OF INFECTIOUS DISEASES 220 (5): 811–19. https://doi.org/10.1093/infdis/jiz171.
Chicago author-date (all authors)
Ibrahim Mahmoud Sayed, Ibrahim, Lieven Verhoye, Claire Montpellier, Florence Abravanel, Jacques Izopet, Laurence Cocquerel, and Philip Meuleman. 2019. “Hepatitis E Virus (HEV) Open Reading Frame 2 Antigen Kinetics in Human-Liver Chimeric Mice and Its Impact on HEV Diagnosis.” JOURNAL OF INFECTIOUS DISEASES 220 (5): 811–819. doi:10.1093/infdis/jiz171.
Vancouver
1.
Ibrahim Mahmoud Sayed I, Verhoye L, Montpellier C, Abravanel F, Izopet J, Cocquerel L, et al. Hepatitis E virus (HEV) open reading frame 2 antigen kinetics in human-liver chimeric mice and its impact on HEV diagnosis. JOURNAL OF INFECTIOUS DISEASES. 2019;220(5):811–9.
IEEE
[1]
I. Ibrahim Mahmoud Sayed et al., “Hepatitis E virus (HEV) open reading frame 2 antigen kinetics in human-liver chimeric mice and its impact on HEV diagnosis,” JOURNAL OF INFECTIOUS DISEASES, vol. 220, no. 5, pp. 811–819, 2019.
@article{8613837,
  abstract     = {{Background. Hepatitis E virus infection (HEV) is an emerging problem in developed countries. Diagnosis of HEV infection is based on the detection of HEV-specific antibodies, viral RNA, and/or antigen (Ag). Humanized mice were previously reported as a model for the study of HEV infection, but published data were focused on the quantification of viral RNA. However, the kinetics of HEV Ag expression during infection remains poorly understood. 
Methods. Plasma specimens and suspensions of fecal specimens from HEV-infected and ribavirin-treated humanized mice were analyzed using HEV antigen-specific enzyme-linked immunosorbent assay, reverse transcription-quantitative polymerase chain reaction analysis, density gradient analysis, and Western blotting. 
Result. Open reading frame 2 (ORF2) Ag was detected in both plasma and stool from HEV-infected mice, and levels increased over time. Contrary to HEV RNA, ORF2 Ag levels were higher in mouse plasma than in stool. Interestingly, ORF2 was detected in plasma from mice that tested negative for HEV RNA in plasma but positive for HEV RNA in stool and was detected after viral clearance in mice that were treated with ribavirin. Plasma density gradient analysis revealed the presence of the noninfectious glycosylated form of ORF2. 
Conclusion: ORF2 Ag can be used as a marker of active HEV infection and for assessment of the effect of antiviral therapy, especially when fecal samples are not available or molecular diagnostic tests are not accessible.}},
  author       = {{Ibrahim Mahmoud Sayed, Ibrahim and Verhoye, Lieven and Montpellier, Claire and Abravanel, Florence and Izopet, Jacques and Cocquerel, Laurence and Meuleman, Philip}},
  issn         = {{0022-1899}},
  journal      = {{JOURNAL OF INFECTIOUS DISEASES}},
  keywords     = {{HEV Ag,humanized mice,ORF2,diagnosis,ribavirin therapy,INFECTION,GENOTYPE,RIBAVIRIN,CAMELS,MARKER,MODEL}},
  language     = {{eng}},
  number       = {{5}},
  pages        = {{811--819}},
  title        = {{Hepatitis E virus (HEV) open reading frame 2 antigen kinetics in human-liver chimeric mice and its impact on HEV diagnosis}},
  url          = {{http://dx.doi.org/10.1093/infdis/jiz171}},
  volume       = {{220}},
  year         = {{2019}},
}

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