Hepatitis E virus persists in the ejaculate of chronically infected men
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Hepatitis E virus persists in the ejaculate of chronically infected men. / Horvatits, Thomas; Wißmann, Jan-Erik; Johne, Reimar; Groschup, Martin H; Gadicherla, Ashish K; Wiesch, Julian Schulze Zur; Eiden, Martin; Todt, Daniel; Reimer, Rudolph; Dähnert, Lisa; Schöbel, Anja; Horvatits, Karoline; Lübke, Rabea; Wolschke, Christine; Ayuk, Francis; Rybczynski, Meike; Lohse, Ansgar W; Addo, Marylyn M; Herker, Eva; Lütgehetmann, Marc; Steinmann, Eike; Pischke, Sven.
In: J HEPATOL, Vol. 75, No. 1, 07.2021, p. 55-63.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Hepatitis E virus persists in the ejaculate of chronically infected men
AU - Horvatits, Thomas
AU - Wißmann, Jan-Erik
AU - Johne, Reimar
AU - Groschup, Martin H
AU - Gadicherla, Ashish K
AU - Wiesch, Julian Schulze Zur
AU - Eiden, Martin
AU - Todt, Daniel
AU - Reimer, Rudolph
AU - Dähnert, Lisa
AU - Schöbel, Anja
AU - Horvatits, Karoline
AU - Lübke, Rabea
AU - Wolschke, Christine
AU - Ayuk, Francis
AU - Rybczynski, Meike
AU - Lohse, Ansgar W
AU - Addo, Marylyn M
AU - Herker, Eva
AU - Lütgehetmann, Marc
AU - Steinmann, Eike
AU - Pischke, Sven
N1 - Copyright © 2021 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
PY - 2021/7
Y1 - 2021/7
N2 - 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.METHODS: 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.RESULTS: 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.CONCLUSIONS: 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.LAY SUMMARY: 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.
AB - 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.METHODS: 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.RESULTS: 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.CONCLUSIONS: 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.LAY SUMMARY: 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.
U2 - 10.1016/j.jhep.2020.12.030
DO - 10.1016/j.jhep.2020.12.030
M3 - SCORING: Journal article
C2 - 33484776
VL - 75
SP - 55
EP - 63
JO - J HEPATOL
JF - J HEPATOL
SN - 0168-8278
IS - 1
ER -
