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The entry inhibitor Myrcludex-B efficiently blocks intrahepatic virus spreading in humanized mice previously infected with hepatitis B virus

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The entry inhibitor Myrcludex-B efficiently blocks intrahepatic virus spreading in humanized mice previously infected with hepatitis B virus. / Volz, Tassilo; Allweiss, Lena; Ben MBarek, Mounira; Warlich, Michael; Lohse, Ansgar W; Pollok, Joerg-Matthias; Alexandrov, Alexander; Urban, Stephan; Petersen, Jörg; Lütgehetmann, Marc; Dandri, Maura.

In: J HEPATOL, Vol. 58, No. 5, 01.05.2013, p. 861-7.

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

Harvard

Volz, T, Allweiss, L, Ben MBarek, M, Warlich, M, Lohse, AW, Pollok, J-M, Alexandrov, A, Urban, S, Petersen, J, Lütgehetmann, M & Dandri, M 2013, 'The entry inhibitor Myrcludex-B efficiently blocks intrahepatic virus spreading in humanized mice previously infected with hepatitis B virus', J HEPATOL, vol. 58, no. 5, pp. 861-7. https://doi.org/10.1016/j.jhep.2012.12.008

APA

Volz, T., Allweiss, L., Ben MBarek, M., Warlich, M., Lohse, A. W., Pollok, J-M., Alexandrov, A., Urban, S., Petersen, J., Lütgehetmann, M., & Dandri, M. (2013). The entry inhibitor Myrcludex-B efficiently blocks intrahepatic virus spreading in humanized mice previously infected with hepatitis B virus. J HEPATOL, 58(5), 861-7. https://doi.org/10.1016/j.jhep.2012.12.008

Vancouver

Volz T, Allweiss L, Ben MBarek M, Warlich M, Lohse AW, Pollok J-M et al. The entry inhibitor Myrcludex-B efficiently blocks intrahepatic virus spreading in humanized mice previously infected with hepatitis B virus. J HEPATOL. 2013 May 1;58(5):861-7. https://doi.org/10.1016/j.jhep.2012.12.008

Bibtex

@article{2b1c758ea4694472beddae72eaadee83,
title = "The entry inhibitor Myrcludex-B efficiently blocks intrahepatic virus spreading in humanized mice previously infected with hepatitis B virus",
abstract = "BACKGROUND & AIMS: Currently approved antivirals rarely cure hepatitis B virus (HBV) infection. Therefore additional therapeutic strategies interfering with other viral replication steps are needed. Using synthetic lipopeptides derived from the HBV envelope protein, we previously demonstrated prevention of de novo HBV infection in vivo. We aimed at investigating the ability of the lipopeptide Myrcludex-B to block HBV spreading post-infection.METHODS: uPA/SCID mice reconstituted with human hepatocytes were infected with HBV. Daily subcutaneous Myrcludex-B administration was initiated either 3 days, 3 weeks or 8 weeks post HBV inoculation. Viral loads were quantitated in serum and liver, and visualized by immunohistochemistry.RESULTS: Myrcludex-B efficiently prevented viral spreading from the initially infected human hepatocytes, as demonstrated by the lack of increase in viremia, antigen levels and amount of HBcAg-positive human hepatocytes determined 6 weeks after treatment. Myrcludex-B efficiently blocked HBV dissemination also when treatment was started in the ramp-up phase of infection, in mice displaying moderate levels of circulating virions (median 3 × 10(6)HBV DNA copies/ml). Notably, after 6 weeks of treatment, not only the amount of HBcAg-positive hepatocytes, but also intrahepatic cccDNA loads, remained comparable to values found in mice sacrificed 3 weeks post-infection. In none of the experimental settings, drug administration affected human hepatocyte half-life or altered virion productivity.CONCLUSIONS: Myrcludex-B efficiently not only prevented HBV spreading from infected human hepatocytes in vivo, but also hindered amplification of the cccDNA pool in initially infected hepatocytes. Administration of an entry inhibitor, possibly used in combination with current HBV drugs, may improve patients' treatment outcome.",
keywords = "Animals, Antiviral Agents, DNA, Viral, Disease Models, Animal, Hepatitis B, Hepatitis B virus, Hepatocytes, Humans, Lipopeptides, Liver, Mice, Mice, SCID, Treatment Outcome, Virus Internalization, Virus Replication",
author = "Tassilo Volz and Lena Allweiss and {Ben MBarek}, Mounira and Michael Warlich and Lohse, {Ansgar W} and Joerg-Matthias Pollok and Alexander Alexandrov and Stephan Urban and J{\"o}rg Petersen and Marc L{\"u}tgehetmann and Maura Dandri",
note = "Copyright {\textcopyright} 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.",
year = "2013",
month = may,
day = "1",
doi = "10.1016/j.jhep.2012.12.008",
language = "English",
volume = "58",
pages = "861--7",
journal = "J HEPATOL",
issn = "0168-8278",
publisher = "Elsevier",
number = "5",

}

RIS

TY - JOUR

T1 - The entry inhibitor Myrcludex-B efficiently blocks intrahepatic virus spreading in humanized mice previously infected with hepatitis B virus

AU - Volz, Tassilo

AU - Allweiss, Lena

AU - Ben MBarek, Mounira

AU - Warlich, Michael

AU - Lohse, Ansgar W

AU - Pollok, Joerg-Matthias

AU - Alexandrov, Alexander

AU - Urban, Stephan

AU - Petersen, Jörg

AU - Lütgehetmann, Marc

AU - Dandri, Maura

N1 - Copyright © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

PY - 2013/5/1

Y1 - 2013/5/1

N2 - BACKGROUND & AIMS: Currently approved antivirals rarely cure hepatitis B virus (HBV) infection. Therefore additional therapeutic strategies interfering with other viral replication steps are needed. Using synthetic lipopeptides derived from the HBV envelope protein, we previously demonstrated prevention of de novo HBV infection in vivo. We aimed at investigating the ability of the lipopeptide Myrcludex-B to block HBV spreading post-infection.METHODS: uPA/SCID mice reconstituted with human hepatocytes were infected with HBV. Daily subcutaneous Myrcludex-B administration was initiated either 3 days, 3 weeks or 8 weeks post HBV inoculation. Viral loads were quantitated in serum and liver, and visualized by immunohistochemistry.RESULTS: Myrcludex-B efficiently prevented viral spreading from the initially infected human hepatocytes, as demonstrated by the lack of increase in viremia, antigen levels and amount of HBcAg-positive human hepatocytes determined 6 weeks after treatment. Myrcludex-B efficiently blocked HBV dissemination also when treatment was started in the ramp-up phase of infection, in mice displaying moderate levels of circulating virions (median 3 × 10(6)HBV DNA copies/ml). Notably, after 6 weeks of treatment, not only the amount of HBcAg-positive hepatocytes, but also intrahepatic cccDNA loads, remained comparable to values found in mice sacrificed 3 weeks post-infection. In none of the experimental settings, drug administration affected human hepatocyte half-life or altered virion productivity.CONCLUSIONS: Myrcludex-B efficiently not only prevented HBV spreading from infected human hepatocytes in vivo, but also hindered amplification of the cccDNA pool in initially infected hepatocytes. Administration of an entry inhibitor, possibly used in combination with current HBV drugs, may improve patients' treatment outcome.

AB - BACKGROUND & AIMS: Currently approved antivirals rarely cure hepatitis B virus (HBV) infection. Therefore additional therapeutic strategies interfering with other viral replication steps are needed. Using synthetic lipopeptides derived from the HBV envelope protein, we previously demonstrated prevention of de novo HBV infection in vivo. We aimed at investigating the ability of the lipopeptide Myrcludex-B to block HBV spreading post-infection.METHODS: uPA/SCID mice reconstituted with human hepatocytes were infected with HBV. Daily subcutaneous Myrcludex-B administration was initiated either 3 days, 3 weeks or 8 weeks post HBV inoculation. Viral loads were quantitated in serum and liver, and visualized by immunohistochemistry.RESULTS: Myrcludex-B efficiently prevented viral spreading from the initially infected human hepatocytes, as demonstrated by the lack of increase in viremia, antigen levels and amount of HBcAg-positive human hepatocytes determined 6 weeks after treatment. Myrcludex-B efficiently blocked HBV dissemination also when treatment was started in the ramp-up phase of infection, in mice displaying moderate levels of circulating virions (median 3 × 10(6)HBV DNA copies/ml). Notably, after 6 weeks of treatment, not only the amount of HBcAg-positive hepatocytes, but also intrahepatic cccDNA loads, remained comparable to values found in mice sacrificed 3 weeks post-infection. In none of the experimental settings, drug administration affected human hepatocyte half-life or altered virion productivity.CONCLUSIONS: Myrcludex-B efficiently not only prevented HBV spreading from infected human hepatocytes in vivo, but also hindered amplification of the cccDNA pool in initially infected hepatocytes. Administration of an entry inhibitor, possibly used in combination with current HBV drugs, may improve patients' treatment outcome.

KW - Animals

KW - Antiviral Agents

KW - DNA, Viral

KW - Disease Models, Animal

KW - Hepatitis B

KW - Hepatitis B virus

KW - Hepatocytes

KW - Humans

KW - Lipopeptides

KW - Liver

KW - Mice

KW - Mice, SCID

KW - Treatment Outcome

KW - Virus Internalization

KW - Virus Replication

U2 - 10.1016/j.jhep.2012.12.008

DO - 10.1016/j.jhep.2012.12.008

M3 - SCORING: Journal article

C2 - 23246506

VL - 58

SP - 861

EP - 867

JO - J HEPATOL

JF - J HEPATOL

SN - 0168-8278

IS - 5

ER -