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Genetic determinants of host- and virus-derived insertions for hepatitis E virus replication

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Genetic determinants of host- and virus-derived insertions for hepatitis E virus replication. / Wißing, Michael Hermann; Meister, Toni Luise; Nocke, Maximilian Klaus; Gömer, André; Masovic, Mejrema; Knegendorf, Leonard; Brüggemann, Yannick; Bader, Verian; Siddharta, Anindya; Bock, Claus-Thomas; Ploss, Alexander; Kenney, Scott P; Winklhofer, Konstanze F; Behrendt, Patrick; Wedemeyer, Heiner; Steinmann, Eike; Todt, Daniel.

In: NAT COMMUN, Vol. 15, No. 1, 06.06.2024, p. 4855.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Wißing, MH, Meister, TL, Nocke, MK, Gömer, A, Masovic, M, Knegendorf, L, Brüggemann, Y, Bader, V, Siddharta, A, Bock, C-T, Ploss, A, Kenney, SP, Winklhofer, KF, Behrendt, P, Wedemeyer, H, Steinmann, E & Todt, D 2024, 'Genetic determinants of host- and virus-derived insertions for hepatitis E virus replication', NAT COMMUN, vol. 15, no. 1, pp. 4855. https://doi.org/10.1038/s41467-024-49219-8

APA

Wißing, M. H., Meister, T. L., Nocke, M. K., Gömer, A., Masovic, M., Knegendorf, L., Brüggemann, Y., Bader, V., Siddharta, A., Bock, C-T., Ploss, A., Kenney, S. P., Winklhofer, K. F., Behrendt, P., Wedemeyer, H., Steinmann, E., & Todt, D. (2024). Genetic determinants of host- and virus-derived insertions for hepatitis E virus replication. NAT COMMUN, 15(1), 4855. https://doi.org/10.1038/s41467-024-49219-8

Vancouver

Wißing MH, Meister TL, Nocke MK, Gömer A, Masovic M, Knegendorf L et al. Genetic determinants of host- and virus-derived insertions for hepatitis E virus replication. NAT COMMUN. 2024 Jun 6;15(1):4855. https://doi.org/10.1038/s41467-024-49219-8

Bibtex

@article{81b8c3cdf365489299ac10e47c19d719,
title = "Genetic determinants of host- and virus-derived insertions for hepatitis E virus replication",
abstract = "Hepatitis E virus (HEV) is a long-neglected RNA virus and the major causative agent of acute viral hepatitis in humans. Recent data suggest that HEV has a very heterogeneous hypervariable region (HVR), which can tolerate major genomic rearrangements. In this study, we identify insertions of previously undescribed sequence snippets in serum samples of a ribavirin treatment failure patient. These insertions increase viral replication while not affecting sensitivity towards ribavirin in a subgenomic replicon assay. All insertions contain a predicted nuclear localization sequence and alanine scanning mutagenesis of lysine residues in the HVR influences viral replication. Sequential replacement of lysine residues additionally alters intracellular localization in a fluorescence dye-coupled construct. Furthermore, distinct sequence patterns outside the HVR are identified as viral determinants that recapitulate the enhancing effect. In conclusion, patient-derived insertions can increase HEV replication and synergistically acting viral determinants in and outside the HVR are described. These results will help to understand the underlying principles of viral adaptation by viral- and host-sequence snatching during the clinical course of infection.",
keywords = "Virus Replication/genetics, Hepatitis E virus/genetics, Humans, Hepatitis E/virology, Ribavirin/pharmacology, Mutagenesis, Insertional, Antiviral Agents/pharmacology, RNA, Viral/genetics, Genome, Viral, Replicon/genetics",
author = "Wi{\ss}ing, {Michael Hermann} and Meister, {Toni Luise} and Nocke, {Maximilian Klaus} and Andr{\'e} G{\"o}mer and Mejrema Masovic and Leonard Knegendorf and Yannick Br{\"u}ggemann and Verian Bader and Anindya Siddharta and Claus-Thomas Bock and Alexander Ploss and Kenney, {Scott P} and Winklhofer, {Konstanze F} and Patrick Behrendt and Heiner Wedemeyer and Eike Steinmann and Daniel Todt",
note = "{\textcopyright} 2024. The Author(s).",
year = "2024",
month = jun,
day = "6",
doi = "10.1038/s41467-024-49219-8",
language = "English",
volume = "15",
pages = "4855",
journal = "NAT COMMUN",
issn = "2041-1723",
publisher = "NATURE PUBLISHING GROUP",
number = "1",

}

RIS

TY - JOUR

T1 - Genetic determinants of host- and virus-derived insertions for hepatitis E virus replication

AU - Wißing, Michael Hermann

AU - Meister, Toni Luise

AU - Nocke, Maximilian Klaus

AU - Gömer, André

AU - Masovic, Mejrema

AU - Knegendorf, Leonard

AU - Brüggemann, Yannick

AU - Bader, Verian

AU - Siddharta, Anindya

AU - Bock, Claus-Thomas

AU - Ploss, Alexander

AU - Kenney, Scott P

AU - Winklhofer, Konstanze F

AU - Behrendt, Patrick

AU - Wedemeyer, Heiner

AU - Steinmann, Eike

AU - Todt, Daniel

N1 - © 2024. The Author(s).

PY - 2024/6/6

Y1 - 2024/6/6

N2 - Hepatitis E virus (HEV) is a long-neglected RNA virus and the major causative agent of acute viral hepatitis in humans. Recent data suggest that HEV has a very heterogeneous hypervariable region (HVR), which can tolerate major genomic rearrangements. In this study, we identify insertions of previously undescribed sequence snippets in serum samples of a ribavirin treatment failure patient. These insertions increase viral replication while not affecting sensitivity towards ribavirin in a subgenomic replicon assay. All insertions contain a predicted nuclear localization sequence and alanine scanning mutagenesis of lysine residues in the HVR influences viral replication. Sequential replacement of lysine residues additionally alters intracellular localization in a fluorescence dye-coupled construct. Furthermore, distinct sequence patterns outside the HVR are identified as viral determinants that recapitulate the enhancing effect. In conclusion, patient-derived insertions can increase HEV replication and synergistically acting viral determinants in and outside the HVR are described. These results will help to understand the underlying principles of viral adaptation by viral- and host-sequence snatching during the clinical course of infection.

AB - Hepatitis E virus (HEV) is a long-neglected RNA virus and the major causative agent of acute viral hepatitis in humans. Recent data suggest that HEV has a very heterogeneous hypervariable region (HVR), which can tolerate major genomic rearrangements. In this study, we identify insertions of previously undescribed sequence snippets in serum samples of a ribavirin treatment failure patient. These insertions increase viral replication while not affecting sensitivity towards ribavirin in a subgenomic replicon assay. All insertions contain a predicted nuclear localization sequence and alanine scanning mutagenesis of lysine residues in the HVR influences viral replication. Sequential replacement of lysine residues additionally alters intracellular localization in a fluorescence dye-coupled construct. Furthermore, distinct sequence patterns outside the HVR are identified as viral determinants that recapitulate the enhancing effect. In conclusion, patient-derived insertions can increase HEV replication and synergistically acting viral determinants in and outside the HVR are described. These results will help to understand the underlying principles of viral adaptation by viral- and host-sequence snatching during the clinical course of infection.

KW - Virus Replication/genetics

KW - Hepatitis E virus/genetics

KW - Humans

KW - Hepatitis E/virology

KW - Ribavirin/pharmacology

KW - Mutagenesis, Insertional

KW - Antiviral Agents/pharmacology

KW - RNA, Viral/genetics

KW - Genome, Viral

KW - Replicon/genetics

U2 - 10.1038/s41467-024-49219-8

DO - 10.1038/s41467-024-49219-8

M3 - SCORING: Journal article

C2 - 38844458

VL - 15

SP - 4855

JO - NAT COMMUN

JF - NAT COMMUN

SN - 2041-1723

IS - 1

ER -