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Murine hepatocytes do not support persistence of Hepatitis D Virus mono-infection in vivo

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Murine hepatocytes do not support persistence of Hepatitis D Virus mono-infection in vivo. / Giersch, Katja; Hermanussen, Lennart; Volz, Tassilo; Kah, Janine; Allweiss, Lena; Casey, John; Sureau, Camille; Dandri, Maura; Lütgehetmann, Marc.

In: LIVER INT, Vol. 41, No. 2, 02.2021, p. 410-419.

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

Harvard

Giersch, K, Hermanussen, L, Volz, T, Kah, J, Allweiss, L, Casey, J, Sureau, C, Dandri, M & Lütgehetmann, M 2021, 'Murine hepatocytes do not support persistence of Hepatitis D Virus mono-infection in vivo', LIVER INT, vol. 41, no. 2, pp. 410-419. https://doi.org/10.1111/liv.14677

APA

Giersch, K., Hermanussen, L., Volz, T., Kah, J., Allweiss, L., Casey, J., Sureau, C., Dandri, M., & Lütgehetmann, M. (2021). Murine hepatocytes do not support persistence of Hepatitis D Virus mono-infection in vivo. LIVER INT, 41(2), 410-419. https://doi.org/10.1111/liv.14677

Vancouver

Giersch K, Hermanussen L, Volz T, Kah J, Allweiss L, Casey J et al. Murine hepatocytes do not support persistence of Hepatitis D Virus mono-infection in vivo. LIVER INT. 2021 Feb;41(2):410-419. https://doi.org/10.1111/liv.14677

Bibtex

@article{2f8c380d1ccf4840a207b81ffd7a1468,
title = "Murine hepatocytes do not support persistence of Hepatitis D Virus mono-infection in vivo",
abstract = "BACKGROUNDS & AIMS: As a result of the limited availability of in vivo models for hepatitis D virus (HDV), treatment options for HDV chronically infected patients are still scant. The discovery of sodium taurocholate cotransporting polypeptide (NTCP) as HDV entry receptor has enabled the development of new infection models.AIM: To comparatively assess the efficacy and persistence of HDV mono-infection in murine and human hepatocytes in vivo.METHODS: Mice with humanized NTCP (hNTCPed84-87 mice) were generated by editing amino acid residues 84-87 of murine NTCP in C57BL/6J mice. HDV infection was assessed in hNTCPed84-87 mice and in immune deficient uPA/SCID/beige (USB) mice, whose livers were reconstituted with human or murine (hNTCPed84-87 ) hepatocytes. Livers were analysed between 5 and 42 days post-HDV inoculation by qRT-PCR, immunofluorescence and RNA in situ hybridization (ISH).RESULTS: hNTCPed84-87 mice could be infected with HDV genotype 1 or 3. ISH analysis demonstrated the presence of antigenomic HDV RNA positive murine hepatocytes with both genotypes, proving initiation of HDV replication. Strikingly, murine hepatocytes cleared HDV within 21 days both in immunocompetent hNTCPed84-87 mice and in immunodeficient USB mice xenografted with murine hepatocytes. In contrast, HDV infection remained stable for at least 42 days in human hepatocytes. Intrinsic innate responses were not enhanced in any of the HDV mono-infected cells and livers.CONCLUSION: These findings suggest that in addition to NTCP, further species-specific factors limit HDV infection efficacy and persistence in murine hepatocytes. Identifying such species barriers may be crucial to develop novel potential therapeutic targets of HDV.",
author = "Katja Giersch and Lennart Hermanussen and Tassilo Volz and Janine Kah and Lena Allweiss and John Casey and Camille Sureau and Maura Dandri and Marc L{\"u}tgehetmann",
note = "{\textcopyright} 2020 The Authors. Liver International published by John Wiley & Sons Ltd.",
year = "2021",
month = feb,
doi = "10.1111/liv.14677",
language = "English",
volume = "41",
pages = "410--419",
journal = "LIVER INT",
issn = "1478-3223",
publisher = "Wiley-Blackwell",
number = "2",

}

RIS

TY - JOUR

T1 - Murine hepatocytes do not support persistence of Hepatitis D Virus mono-infection in vivo

AU - Giersch, Katja

AU - Hermanussen, Lennart

AU - Volz, Tassilo

AU - Kah, Janine

AU - Allweiss, Lena

AU - Casey, John

AU - Sureau, Camille

AU - Dandri, Maura

AU - Lütgehetmann, Marc

N1 - © 2020 The Authors. Liver International published by John Wiley & Sons Ltd.

PY - 2021/2

Y1 - 2021/2

N2 - BACKGROUNDS & AIMS: As a result of the limited availability of in vivo models for hepatitis D virus (HDV), treatment options for HDV chronically infected patients are still scant. The discovery of sodium taurocholate cotransporting polypeptide (NTCP) as HDV entry receptor has enabled the development of new infection models.AIM: To comparatively assess the efficacy and persistence of HDV mono-infection in murine and human hepatocytes in vivo.METHODS: Mice with humanized NTCP (hNTCPed84-87 mice) were generated by editing amino acid residues 84-87 of murine NTCP in C57BL/6J mice. HDV infection was assessed in hNTCPed84-87 mice and in immune deficient uPA/SCID/beige (USB) mice, whose livers were reconstituted with human or murine (hNTCPed84-87 ) hepatocytes. Livers were analysed between 5 and 42 days post-HDV inoculation by qRT-PCR, immunofluorescence and RNA in situ hybridization (ISH).RESULTS: hNTCPed84-87 mice could be infected with HDV genotype 1 or 3. ISH analysis demonstrated the presence of antigenomic HDV RNA positive murine hepatocytes with both genotypes, proving initiation of HDV replication. Strikingly, murine hepatocytes cleared HDV within 21 days both in immunocompetent hNTCPed84-87 mice and in immunodeficient USB mice xenografted with murine hepatocytes. In contrast, HDV infection remained stable for at least 42 days in human hepatocytes. Intrinsic innate responses were not enhanced in any of the HDV mono-infected cells and livers.CONCLUSION: These findings suggest that in addition to NTCP, further species-specific factors limit HDV infection efficacy and persistence in murine hepatocytes. Identifying such species barriers may be crucial to develop novel potential therapeutic targets of HDV.

AB - BACKGROUNDS & AIMS: As a result of the limited availability of in vivo models for hepatitis D virus (HDV), treatment options for HDV chronically infected patients are still scant. The discovery of sodium taurocholate cotransporting polypeptide (NTCP) as HDV entry receptor has enabled the development of new infection models.AIM: To comparatively assess the efficacy and persistence of HDV mono-infection in murine and human hepatocytes in vivo.METHODS: Mice with humanized NTCP (hNTCPed84-87 mice) were generated by editing amino acid residues 84-87 of murine NTCP in C57BL/6J mice. HDV infection was assessed in hNTCPed84-87 mice and in immune deficient uPA/SCID/beige (USB) mice, whose livers were reconstituted with human or murine (hNTCPed84-87 ) hepatocytes. Livers were analysed between 5 and 42 days post-HDV inoculation by qRT-PCR, immunofluorescence and RNA in situ hybridization (ISH).RESULTS: hNTCPed84-87 mice could be infected with HDV genotype 1 or 3. ISH analysis demonstrated the presence of antigenomic HDV RNA positive murine hepatocytes with both genotypes, proving initiation of HDV replication. Strikingly, murine hepatocytes cleared HDV within 21 days both in immunocompetent hNTCPed84-87 mice and in immunodeficient USB mice xenografted with murine hepatocytes. In contrast, HDV infection remained stable for at least 42 days in human hepatocytes. Intrinsic innate responses were not enhanced in any of the HDV mono-infected cells and livers.CONCLUSION: These findings suggest that in addition to NTCP, further species-specific factors limit HDV infection efficacy and persistence in murine hepatocytes. Identifying such species barriers may be crucial to develop novel potential therapeutic targets of HDV.

U2 - 10.1111/liv.14677

DO - 10.1111/liv.14677

M3 - SCORING: Journal article

C2 - 32997847

VL - 41

SP - 410

EP - 419

JO - LIVER INT

JF - LIVER INT

SN - 1478-3223

IS - 2

ER -