DOI: 10.1128/jvi.75.11.5108-5118.2001. Transfer of Hepatitis B Virus Genome by Adenovirus Vectors into Cultured Cells and Mice: Crossing the Species Barrier

Transfer of Hepatitis B Virus Genome by Adenovirus Vectors into Cultured Cells and Mice: Crossing the Species Barrier

10.1128/jvi.75.11.5108-5118.2001

Crossref journal-article

American Society for Microbiology

Journal of Virology (235)

Abstract

ABSTRACTFor the study of hepatitis B virus infection, no permissive cell line or small animal is available. Stably transfected cell lines and transgenic mice which contain hepadnavirus genomes produce virus, but—unlike in natural infection—from an integrated viral transcription template. To transfer hepadnavirus genomes across the species barrier, we developed adenovirus vectors in which 1.3-fold-overlength human and duck hepatitis B virus genomes were inserted. The adenovirus-mediated genome transfer efficiently initiated hepadnavirus replication from an extrachromosomal template in established cell lines, in primary hepatocytes from various species, and in the livers of mice. Following the transfer, hepatitis B virus proteins, genomic RNA, and all replicative DNA intermediates were detected. Detection of covalently closed circular DNA in hepatoma cell lines and in primary hepatocytes indicated that an intracellular replication cycle independent from the transferred linear viral genome was established. High-titer hepatitis B virions were released into the culture medium of hepatoma cells and the various primary hepatocytes. In addition, infectious virions were secreted into the sera of mice. In conclusion, adenovirus-mediated genome transfer initiated efficient hepatitis B virus replication in cultured liver cells and in the experimental animals from an extrachromosomal template. This will allow development of small-animal systems of hepatitis B virus infection and will facilitate study of pathogenicity of wild-type and mutant viruses as well as of virus-host interaction and new therapeutic approaches.

Bibliography

Sprinzl, M. F., Oberwinkler, H., Schaller, H., & Protzer, U. (2001). Transfer of Hepatitis B Virus Genome by Adenovirus Vectors into Cultured Cells and Mice: Crossing the Species Barrier. Journal of Virology, 75(11), 5108â5118.

Authors 4

Martin Franz Sprinzl (first)
Heike Oberwinkler (additional)
Heinz Schaller (additional)
Ulrike Protzer (additional)

References 60 Referenced 131

10.1038/sj.gt.3301027
10.1128/jvi.64.7.3319-3330.1990
10.1073/pnas.93.6.2348
10.1016/0958-1669(95)80097-2
10.1002/hep.510310126
10.1016/S0165-2478(97)00049-7
10.1128/jvi.64.7.3249-3258.1990
10.1002/hep.510280432
10.1128/AAC.43.8.2017
10.1006/viro.1996.8422
10.1038/8462
10.1128/jvi.62.4.1408-1415.1988
10.1016/0016-5085(94)90700-5
10.1002/hep.1840100410
Ganem D. Hepadnaviridae: the viruses and their replication Fields virology 3rd ed. Fields B. N. Knipe D. M. Howley P. M. 2 1996 2703 2737 Lippincott-Raven Publishers Philadelphia, Pa / Fields virology / Hepadnaviridae: the viruses and their replication by Ganem D. (1996)
10.1006/viro.1993.1069
10.1073/pnas.93.10.4589
10.1128/jvi.69.10.6158-6169.1995
10.1126/science.284.5415.825
10.1073/pnas.95.5.2509
10.1128/jvi.52.2.396-402.1984
10.1089/10430340050015941
10.1073/pnas.92.22.10099
10.1038/sj.gt.3300607
10.1056/NEJM199701303360507
10.1055/s-2007-1007097
10.1073/pnas.94.24.12744
10.1053/gast.1997.v113.pm9352870
10.1128/JVI.72.7.5573-5578.1998
10.1089/hum.1993.4.4-403
10.1006/bbrc.1999.0954
10.1515/bchm3.1996.377.3.187
10.1128/JVI.74.24.11472-11478.2000
10.1128/jvi.49.3.782-792.1984
10.1111/j.1365-2893.1996.tb00047.x
10.1056/NEJM199605303342202
10.1002/j.1460-2075.1996.tb00614.x
10.1038/73187
10.1038/282575a0
10.1073/pnas.95.1.310
10.1073/pnas.96.19.10818
10.1016/S0091-679X(08)60381-7
10.1159/000150418
10.1128/jvi.61.7.2280-2285.1987
10.1128/jvi.61.12.3701-3709.1987
Schödel F. Weimer T. Fernholz D. Schneider R. Sprengel R. Wildner G. Will H. The biology of avian hepatitis B viruses Molecular biology of the hepatitis B virus. McLachlan A. 1991 53 80 CRC Press Boca Raton Fla (10.1201/9781351074759-3)
10.1073/pnas.84.4.1005
10.1128/jvi.52.3.932-937.1984
10.1016/0092-8674(82)90157-X
10.1128/jvi.64.6.2819-2824.1990
10.1128/jvi.65.3.1310-1317.1991
10.1016/0092-8674(86)90364-8
10.1073/pnas.92.5.1470
10.1128/jvi.58.1.17-25.1986
Walter E. Keist R. Niederost B. Pult I. Blum H. E. Hepatitis B virus infection of Tupaia hepatocytes in vitro and in vivo.Hepatology 24 1996 1 5 (10.1002/hep.510240101) / Hepatology / Hepatitis B virus infection of Tupaia hepatocytes in vitro and in vivo by Walter E. (1996)
10.1073/pnas.82.3.891
World Health Organization Viral Hepatitis Prevention Board: prevention and control of hepatitis B in the community.W. H. O. Communicable Ser. 1 1996 1 26 / W. H. O. Communicable Ser. / Viral Hepatitis Prevention Board: prevention and control of hepatitis B in the community by World Health Organization (1996)
10.1007/BF01261404
10.1016/S0166-3542(99)00056-X
10.1136/bmj.319.7213.799

Dates

Type	When
Created	23 years, 1 month ago (July 27, 2002, 5:55 a.m.)
Deposited	8 months, 3 weeks ago (Dec. 8, 2024, 2:48 p.m.)
Indexed	1 month ago (July 30, 2025, 11:29 a.m.)
Issued	24 years, 2 months ago (June 1, 2001)
Published	24 years, 2 months ago (June 1, 2001)
Published Print	24 years, 2 months ago (June 1, 2001)

Funders 0

None

BibTeX

@article{Sprinzl_2001, title={Transfer of Hepatitis B Virus Genome by Adenovirus Vectors into Cultured Cells and Mice: Crossing the Species Barrier}, volume={75}, ISSN={1098-5514}, url={http://dx.doi.org/10.1128/jvi.75.11.5108-5118.2001}, DOI={10.1128/jvi.75.11.5108-5118.2001}, number={11}, journal={Journal of Virology}, publisher={American Society for Microbiology}, author={Sprinzl, Martin Franz and Oberwinkler, Heike and Schaller, Heinz and Protzer, Ulrike}, year={2001}, month=jun, pages={5108–5118} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        7,
        30
      ]
    ],
    "date-time": "2025-07-30T15:29:45Z",
    "timestamp": 1753889385968,
    "version": "3.30.1"
  },
  "reference-count": 60,
  "publisher": "American Society for Microbiology",
  "issue": "11",
  "license": [
    {
      "start": {
        "date-parts": [
          [
            2001,
            6,
            1
          ]
        ],
        "date-time": "2001-06-01T00:00:00Z",
        "timestamp": 991353600000
      },
      "content-version": "tdm",
      "delay-in-days": 0,
      "URL": "https://journals.asm.org/non-commercial-tdm-license"
    }
  ],
  "content-domain": {
    "domain": [
      "journals.asm.org"
    ],
    "crossmark-restriction": true
  },
  "published-print": {
    "date-parts": [
      [
        2001,
        6
      ]
    ]
  },
  "abstract": "<jats:title>ABSTRACT</jats:title><jats:p>For the study of hepatitis B virus infection, no permissive cell line or small animal is available. Stably transfected cell lines and transgenic mice which contain hepadnavirus genomes produce virus, but\u2014unlike in natural infection\u2014from an integrated viral transcription template. To transfer hepadnavirus genomes across the species barrier, we developed adenovirus vectors in which 1.3-fold-overlength human and duck hepatitis B virus genomes were inserted. The adenovirus-mediated genome transfer efficiently initiated hepadnavirus replication from an extrachromosomal template in established cell lines, in primary hepatocytes from various species, and in the livers of mice. Following the transfer, hepatitis B virus proteins, genomic RNA, and all replicative DNA intermediates were detected. Detection of covalently closed circular DNA in hepatoma cell lines and in primary hepatocytes indicated that an intracellular replication cycle independent from the transferred linear viral genome was established. High-titer hepatitis B virions were released into the culture medium of hepatoma cells and the various primary hepatocytes. In addition, infectious virions were secreted into the sera of mice. In conclusion, adenovirus-mediated genome transfer initiated efficient hepatitis B virus replication in cultured liver cells and in the experimental animals from an extrachromosomal template. This will allow development of small-animal systems of hepatitis B virus infection and will facilitate study of pathogenicity of wild-type and mutant viruses as well as of virus-host interaction and new therapeutic approaches.</jats:p>",
  "DOI": "10.1128/jvi.75.11.5108-5118.2001",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2002,
        7,
        27
      ]
    ],
    "date-time": "2002-07-27T09:55:53Z",
    "timestamp": 1027763753000
  },
  "page": "5108-5118",
  "update-policy": "https://doi.org/10.1128/asmj-crossmark-policy-page",
  "source": "Crossref",
  "is-referenced-by-count": 131,
  "title": "Transfer of Hepatitis B Virus Genome by Adenovirus Vectors into Cultured Cells and Mice: Crossing the Species Barrier",
  "prefix": "10.1128",
  "volume": "75",
  "author": [
    {
      "given": "Martin Franz",
      "family": "Sprinzl",
      "sequence": "first",
      "affiliation": [
        {
          "name": "<!--label omitted: 1-->Zentrum fu\u0308r Molekulare Biologie Heidelberg (ZMBH), University of Heidelberg, D-69120 Heidelberg, Federal Republic of Germany"
        }
      ]
    },
    {
      "given": "Heike",
      "family": "Oberwinkler",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "<!--label omitted: 1-->Zentrum fu\u0308r Molekulare Biologie Heidelberg (ZMBH), University of Heidelberg, D-69120 Heidelberg, Federal Republic of Germany"
        }
      ]
    },
    {
      "given": "Heinz",
      "family": "Schaller",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "<!--label omitted: 1-->Zentrum fu\u0308r Molekulare Biologie Heidelberg (ZMBH), University of Heidelberg, D-69120 Heidelberg, Federal Republic of Germany"
        }
      ]
    },
    {
      "given": "Ulrike",
      "family": "Protzer",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "<!--label omitted: 1-->Zentrum fu\u0308r Molekulare Biologie Heidelberg (ZMBH), University of Heidelberg, D-69120 Heidelberg, Federal Republic of Germany"
        }
      ]
    }
  ],
  "member": "235",
  "reference": [
    {
      "key": "e_1_3_2_2_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/sj.gt.3301027"
    },
    {
      "key": "e_1_3_2_3_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/jvi.64.7.3319-3330.1990"
    },
    {
      "key": "e_1_3_2_4_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.93.6.2348"
    },
    {
      "key": "e_1_3_2_5_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0958-1669(95)80097-2"
    },
    {
      "key": "e_1_3_2_6_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/hep.510310126"
    },
    {
      "key": "e_1_3_2_7_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0165-2478(97)00049-7"
    },
    {
      "key": "e_1_3_2_8_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/jvi.64.7.3249-3258.1990"
    },
    {
      "key": "e_1_3_2_9_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/hep.510280432"
    },
    {
      "key": "e_1_3_2_10_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/AAC.43.8.2017"
    },
    {
      "key": "e_1_3_2_11_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1006/viro.1996.8422"
    },
    {
      "key": "e_1_3_2_12_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/8462"
    },
    {
      "key": "e_1_3_2_13_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/jvi.62.4.1408-1415.1988"
    },
    {
      "key": "e_1_3_2_14_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0016-5085(94)90700-5"
    },
    {
      "key": "e_1_3_2_15_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/hep.1840100410"
    },
    {
      "key": "e_1_3_2_16_2",
      "first-page": "2703",
      "article-title": "Hepadnaviridae: the viruses and their replication",
      "volume": "2",
      "author": "Ganem D.",
      "year": "1996",
      "unstructured": "Ganem D. Hepadnaviridae: the viruses and their replication Fields virology 3rd ed. Fields B. N. Knipe D. M. Howley P. M. 2 1996 2703 2737 Lippincott-Raven Publishers Philadelphia, Pa",
      "journal-title": "Fields virology"
    },
    {
      "key": "e_1_3_2_17_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1006/viro.1993.1069"
    },
    {
      "key": "e_1_3_2_18_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.93.10.4589"
    },
    {
      "key": "e_1_3_2_19_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/jvi.69.10.6158-6169.1995"
    },
    {
      "key": "e_1_3_2_20_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.284.5415.825"
    },
    {
      "key": "e_1_3_2_21_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.95.5.2509"
    },
    {
      "key": "e_1_3_2_22_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/jvi.52.2.396-402.1984"
    },
    {
      "key": "e_1_3_2_23_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1089/10430340050015941"
    },
    {
      "key": "e_1_3_2_24_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.92.22.10099"
    },
    {
      "key": "e_1_3_2_25_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/sj.gt.3300607"
    },
    {
      "key": "e_1_3_2_26_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1056/NEJM199701303360507"
    },
    {
      "key": "e_1_3_2_27_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1055/s-2007-1007097"
    },
    {
      "key": "e_1_3_2_28_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.94.24.12744"
    },
    {
      "key": "e_1_3_2_29_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1053/gast.1997.v113.pm9352870"
    },
    {
      "key": "e_1_3_2_30_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/JVI.72.7.5573-5578.1998"
    },
    {
      "key": "e_1_3_2_31_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1089/hum.1993.4.4-403"
    },
    {
      "key": "e_1_3_2_32_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1006/bbrc.1999.0954"
    },
    {
      "key": "e_1_3_2_33_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1515/bchm3.1996.377.3.187"
    },
    {
      "key": "e_1_3_2_34_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/JVI.74.24.11472-11478.2000"
    },
    {
      "key": "e_1_3_2_35_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/jvi.49.3.782-792.1984"
    },
    {
      "key": "e_1_3_2_36_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1111/j.1365-2893.1996.tb00047.x"
    },
    {
      "key": "e_1_3_2_37_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1056/NEJM199605303342202"
    },
    {
      "key": "e_1_3_2_38_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/j.1460-2075.1996.tb00614.x"
    },
    {
      "key": "e_1_3_2_39_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/73187"
    },
    {
      "key": "e_1_3_2_40_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/282575a0"
    },
    {
      "key": "e_1_3_2_41_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.95.1.310"
    },
    {
      "key": "e_1_3_2_42_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.96.19.10818"
    },
    {
      "key": "e_1_3_2_43_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0091-679X(08)60381-7"
    },
    {
      "key": "e_1_3_2_44_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1159/000150418"
    },
    {
      "key": "e_1_3_2_45_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/jvi.61.7.2280-2285.1987"
    },
    {
      "key": "e_1_3_2_46_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/jvi.61.12.3701-3709.1987"
    },
    {
      "key": "e_1_3_2_47_2",
      "doi-asserted-by": "crossref",
      "unstructured": "Sch\u00f6del F. Weimer T. Fernholz D. Schneider R. Sprengel R. Wildner G. Will H. The biology of avian hepatitis B viruses Molecular biology of the hepatitis B virus. McLachlan A. 1991 53 80 CRC Press Boca Raton Fla",
      "DOI": "10.1201/9781351074759-3"
    },
    {
      "key": "e_1_3_2_48_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.84.4.1005"
    },
    {
      "key": "e_1_3_2_49_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/jvi.52.3.932-937.1984"
    },
    {
      "key": "e_1_3_2_50_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0092-8674(82)90157-X"
    },
    {
      "key": "e_1_3_2_51_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/jvi.64.6.2819-2824.1990"
    },
    {
      "key": "e_1_3_2_52_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/jvi.65.3.1310-1317.1991"
    },
    {
      "key": "e_1_3_2_53_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0092-8674(86)90364-8"
    },
    {
      "key": "e_1_3_2_54_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.92.5.1470"
    },
    {
      "key": "e_1_3_2_55_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/jvi.58.1.17-25.1986"
    },
    {
      "key": "e_1_3_2_56_2",
      "doi-asserted-by": "crossref",
      "first-page": "1",
      "DOI": "10.1002/hep.510240101",
      "article-title": "Hepatitis B virus infection of Tupaia hepatocytes in vitro and in vivo",
      "volume": "24",
      "author": "Walter E.",
      "year": "1996",
      "unstructured": "Walter E. Keist R. Niederost B. Pult I. Blum H. E. Hepatitis B virus infection of Tupaia hepatocytes in vitro and in vivo.Hepatology 24 1996 1 5",
      "journal-title": "Hepatology"
    },
    {
      "key": "e_1_3_2_57_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.82.3.891"
    },
    {
      "key": "e_1_3_2_58_2",
      "first-page": "1",
      "article-title": "Viral Hepatitis Prevention Board: prevention and control of hepatitis B in the community",
      "volume": "1",
      "author": "World Health Organization",
      "year": "1996",
      "unstructured": "World Health Organization Viral Hepatitis Prevention Board: prevention and control of hepatitis B in the community.W. H. O. Communicable Ser. 1 1996 1 26",
      "journal-title": "W. H. O. Communicable Ser."
    },
    {
      "key": "e_1_3_2_59_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1007/BF01261404"
    },
    {
      "key": "e_1_3_2_60_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0166-3542(99)00056-X"
    },
    {
      "key": "e_1_3_2_61_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1136/bmj.319.7213.799"
    }
  ],
  "container-title": "Journal of Virology",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://journals.asm.org/doi/pdf/10.1128/JVI.75.11.5108-5118.2001",
      "content-type": "application/pdf",
      "content-version": "vor",
      "intended-application": "text-mining"
    },
    {
      "URL": "https://journals.asm.org/doi/pdf/10.1128/JVI.75.11.5108-5118.2001",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2024,
        12,
        8
      ]
    ],
    "date-time": "2024-12-08T19:48:10Z",
    "timestamp": 1733687290000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://journals.asm.org/doi/10.1128/JVI.75.11.5108-5118.2001"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        2001,
        6
      ]
    ]
  },
  "references-count": 60,
  "journal-issue": {
    "issue": "11",
    "published-print": {
      "date-parts": [
        [
          2001,
          6
        ]
      ]
    }
  },
  "alternative-id": [
    "10.1128/JVI.75.11.5108-5118.2001"
  ],
  "URL": "http://dx.doi.org/10.1128/JVI.75.11.5108-5118.2001",
  "relation": {},
  "ISSN": [
    "0022-538X",
    "1098-5514"
  ],
  "subject": [],
  "container-title-short": "J Virol",
  "published": {
    "date-parts": [
      [
        2001,
        6
      ]
    ]
  },
  "assertion": [
    {
      "value": "2000-11-10",
      "order": 0,
      "name": "received",
      "label": "Received",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    },
    {
      "value": "2001-03-01",
      "order": 1,
      "name": "accepted",
      "label": "Accepted",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    },
    {
      "value": "2001-06-01",
      "order": 2,
      "name": "published",
      "label": "Published",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    }
  ]
}