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Prevention of hepatitis B virus infection in vivo by entry inhibitors derived from the large envelope protein
360 million people are chronically infected with the human hepatitis B virus (HBV) and are consequently prone to develop liver cirrhosis and hepatocellular carcinoma. As approved therapeutic regimens-which modulate patients' antiviral defenses or inhibit the viral reverse transcriptase-are gene...
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| Published in: | Nature biotechnology 2008-03, Vol.26 (3), p.335-341 |
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| Main Authors: | , , , , , , , , , , , |
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| container_end_page | 341 |
| container_issue | 3 |
| container_start_page | 335 |
| container_title | Nature biotechnology |
| container_volume | 26 |
| creator | Urban, Stephan Petersen, Joerg Dandri, Maura Mier, Walter Lütgehetmann, Marc Volz, Tassilo von Weizsäcker, Fritz Haberkorn, Uwe Fischer, Lutz Pollok, Joerg-Matthias Erbes, Berit Seitz, Stefan |
| description | 360 million people are chronically infected with the human hepatitis B virus (HBV) and are consequently prone to develop liver cirrhosis and hepatocellular carcinoma. As approved therapeutic regimens-which modulate patients' antiviral defenses or inhibit the viral reverse transcriptase-are generally noncurative, strategies interfering with other HBV replication steps are required. Expanding on our demonstration that acylated peptides derived from the large HBV envelope protein block virus entry in vitro, we show their applicability to prevent HBV or woolly monkey hepatitis B virus infection in vivo, using immunodeficient urokinase-type plasminogen activator (uPA) mice repopulated with primary human or Tupaia belangeri hepatocytes. Accumulation of the peptides in the liver, their extraordinary inhibitory potency and specific mode of action permit subcutaneous delivery at very low doses. Inhibition of hepadnavirus entry thus constitutes a therapeutic approach to prevent primary HBV infection, such as after liver transplantation, and might also restrain virus spread in chronically infected patients. |
| doi_str_mv | 10.1038/nbt1389 |
| format | article |
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As approved therapeutic regimens-which modulate patients' antiviral defenses or inhibit the viral reverse transcriptase-are generally noncurative, strategies interfering with other HBV replication steps are required. Expanding on our demonstration that acylated peptides derived from the large HBV envelope protein block virus entry in vitro, we show their applicability to prevent HBV or woolly monkey hepatitis B virus infection in vivo, using immunodeficient urokinase-type plasminogen activator (uPA) mice repopulated with primary human or Tupaia belangeri hepatocytes. Accumulation of the peptides in the liver, their extraordinary inhibitory potency and specific mode of action permit subcutaneous delivery at very low doses. Inhibition of hepadnavirus entry thus constitutes a therapeutic approach to prevent primary HBV infection, such as after liver transplantation, and might also restrain virus spread in chronically infected patients.</description><identifier>ISSN: 1087-0156</identifier><identifier>EISSN: 1546-1696</identifier><identifier>DOI: 10.1038/nbt1389</identifier><identifier>PMID: 18297057</identifier><identifier>CODEN: NABIF9</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>Acylation ; Agriculture ; Amino Acid Sequence ; Animals ; Atelinae - virology ; Bioinformatics ; Biological and medical sciences ; Biomedical and Life Sciences ; Biomedical Engineering/Biotechnology ; Biomedicine ; Biotechnology ; Disease prevention ; DNA-Binding Proteins - genetics ; Fundamental and applied biological sciences. Psychology ; Genetic aspects ; Health aspects ; Health. Pharmaceutical industry ; Hepadnavirus ; Hepatitis ; Hepatitis B ; Hepatitis B - prevention & control ; Hepatitis B - virology ; Hepatitis B Surface Antigens - chemistry ; Hepatitis B virus ; Hepatitis B virus - drug effects ; Hepatitis B virus - physiology ; Hepatocytes - cytology ; Hepatocytes - metabolism ; Humans ; Industrial applications and implications. Economical aspects ; Infections ; Inhibitor drugs ; letter ; Life Sciences ; Liver ; Liver - metabolism ; Liver - virology ; Liver transplantation ; Male ; Membrane proteins ; Mice ; Miscellaneous ; Mode of action ; Peptides ; Prevention ; Proteins ; Risk factors ; Rodents ; Tissue Distribution ; Tissue plasminogen activator ; Transplantation, Heterologous ; Tupaia ; Tupaia belangeri ; Urokinase-Type Plasminogen Activator - genetics ; Viral Envelope Proteins - administration & dosage ; Viral Envelope Proteins - chemistry ; Viral Envelope Proteins - pharmacokinetics ; Viral Envelope Proteins - pharmacology ; Viruses</subject><ispartof>Nature biotechnology, 2008-03, Vol.26 (3), p.335-341</ispartof><rights>Springer Nature America, Inc. 2008</rights><rights>2008 INIST-CNRS</rights><rights>COPYRIGHT 2008 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Mar 2008</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c595t-e22aae3061d28751b9ce62da89c5363db585b85526eead53ba298acab7d8fd343</citedby><cites>FETCH-LOGICAL-c595t-e22aae3061d28751b9ce62da89c5363db585b85526eead53ba298acab7d8fd343</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,2727,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20414238$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18297057$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Urban, Stephan</creatorcontrib><creatorcontrib>Petersen, Joerg</creatorcontrib><creatorcontrib>Dandri, Maura</creatorcontrib><creatorcontrib>Mier, Walter</creatorcontrib><creatorcontrib>Lütgehetmann, Marc</creatorcontrib><creatorcontrib>Volz, Tassilo</creatorcontrib><creatorcontrib>von Weizsäcker, Fritz</creatorcontrib><creatorcontrib>Haberkorn, Uwe</creatorcontrib><creatorcontrib>Fischer, Lutz</creatorcontrib><creatorcontrib>Pollok, Joerg-Matthias</creatorcontrib><creatorcontrib>Erbes, Berit</creatorcontrib><creatorcontrib>Seitz, Stefan</creatorcontrib><title>Prevention of hepatitis B virus infection in vivo by entry inhibitors derived from the large envelope protein</title><title>Nature biotechnology</title><addtitle>Nat Biotechnol</addtitle><addtitle>Nat Biotechnol</addtitle><description>360 million people are chronically infected with the human hepatitis B virus (HBV) and are consequently prone to develop liver cirrhosis and hepatocellular carcinoma. As approved therapeutic regimens-which modulate patients' antiviral defenses or inhibit the viral reverse transcriptase-are generally noncurative, strategies interfering with other HBV replication steps are required. Expanding on our demonstration that acylated peptides derived from the large HBV envelope protein block virus entry in vitro, we show their applicability to prevent HBV or woolly monkey hepatitis B virus infection in vivo, using immunodeficient urokinase-type plasminogen activator (uPA) mice repopulated with primary human or Tupaia belangeri hepatocytes. Accumulation of the peptides in the liver, their extraordinary inhibitory potency and specific mode of action permit subcutaneous delivery at very low doses. Inhibition of hepadnavirus entry thus constitutes a therapeutic approach to prevent primary HBV infection, such as after liver transplantation, and might also restrain virus spread in chronically infected patients.</description><subject>Acylation</subject><subject>Agriculture</subject><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Atelinae - virology</subject><subject>Bioinformatics</subject><subject>Biological and medical sciences</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedical Engineering/Biotechnology</subject><subject>Biomedicine</subject><subject>Biotechnology</subject><subject>Disease prevention</subject><subject>DNA-Binding Proteins - genetics</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Genetic aspects</subject><subject>Health aspects</subject><subject>Health. Pharmaceutical industry</subject><subject>Hepadnavirus</subject><subject>Hepatitis</subject><subject>Hepatitis B</subject><subject>Hepatitis B - prevention & control</subject><subject>Hepatitis B - virology</subject><subject>Hepatitis B Surface Antigens - chemistry</subject><subject>Hepatitis B virus</subject><subject>Hepatitis B virus - drug effects</subject><subject>Hepatitis B virus - physiology</subject><subject>Hepatocytes - cytology</subject><subject>Hepatocytes - metabolism</subject><subject>Humans</subject><subject>Industrial applications and implications. 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protein</atitle><jtitle>Nature biotechnology</jtitle><stitle>Nat Biotechnol</stitle><addtitle>Nat Biotechnol</addtitle><date>2008-03-01</date><risdate>2008</risdate><volume>26</volume><issue>3</issue><spage>335</spage><epage>341</epage><pages>335-341</pages><issn>1087-0156</issn><eissn>1546-1696</eissn><coden>NABIF9</coden><abstract>360 million people are chronically infected with the human hepatitis B virus (HBV) and are consequently prone to develop liver cirrhosis and hepatocellular carcinoma. As approved therapeutic regimens-which modulate patients' antiviral defenses or inhibit the viral reverse transcriptase-are generally noncurative, strategies interfering with other HBV replication steps are required. Expanding on our demonstration that acylated peptides derived from the large HBV envelope protein block virus entry in vitro, we show their applicability to prevent HBV or woolly monkey hepatitis B virus infection in vivo, using immunodeficient urokinase-type plasminogen activator (uPA) mice repopulated with primary human or Tupaia belangeri hepatocytes. Accumulation of the peptides in the liver, their extraordinary inhibitory potency and specific mode of action permit subcutaneous delivery at very low doses. Inhibition of hepadnavirus entry thus constitutes a therapeutic approach to prevent primary HBV infection, such as after liver transplantation, and might also restrain virus spread in chronically infected patients.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>18297057</pmid><doi>10.1038/nbt1389</doi><tpages>7</tpages></addata></record> |
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| ispartof | Nature biotechnology, 2008-03, Vol.26 (3), p.335-341 |
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| subjects | Acylation Agriculture Amino Acid Sequence Animals Atelinae - virology Bioinformatics Biological and medical sciences Biomedical and Life Sciences Biomedical Engineering/Biotechnology Biomedicine Biotechnology Disease prevention DNA-Binding Proteins - genetics Fundamental and applied biological sciences. Psychology Genetic aspects Health aspects Health. Pharmaceutical industry Hepadnavirus Hepatitis Hepatitis B Hepatitis B - prevention & control Hepatitis B - virology Hepatitis B Surface Antigens - chemistry Hepatitis B virus Hepatitis B virus - drug effects Hepatitis B virus - physiology Hepatocytes - cytology Hepatocytes - metabolism Humans Industrial applications and implications. Economical aspects Infections Inhibitor drugs letter Life Sciences Liver Liver - metabolism Liver - virology Liver transplantation Male Membrane proteins Mice Miscellaneous Mode of action Peptides Prevention Proteins Risk factors Rodents Tissue Distribution Tissue plasminogen activator Transplantation, Heterologous Tupaia Tupaia belangeri Urokinase-Type Plasminogen Activator - genetics Viral Envelope Proteins - administration & dosage Viral Envelope Proteins - chemistry Viral Envelope Proteins - pharmacokinetics Viral Envelope Proteins - pharmacology Viruses |
| title | Prevention of hepatitis B virus infection in vivo by entry inhibitors derived from the large envelope protein |
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