DOI: 10.1002/hep.510280432. Hepatitis B virus replication in human HepG2 cells mediated by hepatitis B virus recombinant baculovirus

Hepatitis B virus replication in human HepG2 cells mediated by hepatitis B virus recombinant baculovirus

10.1002/hep.510280432

Crossref journal-article

Ovid Technologies (Wolters Kluwer Health)

Hepatology (276)

Abstract

A novel transient mechanism for studying hepatitis B virus (HBV) gene expression and replication using recombinant HBV baculovirus to deliver the HBV genome to HepG2 cells was generated. In HBV baculovirus infected HepG2 cells, HBV transcripts, and intracellular and secreted HBV antigens are produced; replication occurs as evidenced by the presence of high levels of intracellular replicative intermediates and protected HBV DNA in the medium. Density-gradient analysis of extracellular HBV DNA indicated that the DNA was contained predominantly in enveloped HBV virions. Covalently closed circular (CCC) DNA is present indicating that, in this system, HBV core particles are capable of delivering newly synthesized HBV genomes back into the nuclei of infected cells. HBV gene expression is driven exclusively from endogenous promoters. Levels of HBV gene expression and replication can be achieved in HBV baculovirus-infected HepG2 cells which far exceed levels found in HepG2 2.2.15 cells. HBV baculovirus infection of HepG2 cells lends itself readily to experimental manipulation as follows: 1) HBV expression can be initiated any time relative to seeding of HepG2 cells; 2) levels of HBV replication can be regulated over a wide range simply by changing the baculovirus multiplicity of infection; 3) HBV replication is readily detectable by one day post infection with HBV baculovirus and persists at least through day eleven post infection; and (4) the transient nature of the infection can be extended and/or enhanced by superinfecting the cultures. We conclude that infection of HepG2 cells by HBV recombinant baculovirus represents a simple to use and highly flexible system for studying the effects of antivirals and/or cytokines on HBV production and for understanding HBV replication and pathogenesis at the molecular level.

Bibliography

Delaney, W. E., & Isom, H. C. (1998). Hepatitis B virus replication in human HepG2 cells mediated by hepatitis B virus recombinant baculovirus. Hepatology, 28(4), 1134â1146.

Authors 2

William E. Delaney (first)
Harriet C. Isom (additional)

References 54 Referenced 123

10.1016/S0140-6736(81)90585-7 / Lancet by Beasley (1981)
10.1128/JVI.58.1.17-25.1986 / J Virol by Tuttleman (1986)
{'key': 'BIB3', 'first-page': '51', 'volume': '55', 'author': 'Tyler', 'year': '1986', 'journal-title': 'Lab Invest'} / Lab Invest by Tyler (1986)
10.1002/jmv.1890150402 / J Med Virol by Sprengel (1985)
10.1006/viro.1996.8422 / Virology by Di (1997)
10.1073/pnas.84.4.1005 / Proc Nat Acad Sci by Sells (1987)
10.1073/pnas.84.2.444 / Proc Nat Acad Sci by Tsurimoto (1987)
10.1006/viro.1996.0049 / Virology by Weiss (1996)
10.1016/0092-8674(86)90602-1 / Cell by Tuttleman (1986)
10.1038/286533a0 / Nature by Brechot (1980)
10.1101/gad.1.8.773 / Genes Devel by Nagaya (1987)
10.1159/000149278 / Intervirology by Matthews (1982)
10.1128/MCB.4.3.399 / Mol Cell Biol by Pennock (1984)
10.1146/annurev.mi.45.100191.000441 / Ann Rev Micro by Wood (1991)
10.1089/hum.1996.7.16-1937 / Hum Gene Ther by Sandig (1996)
10.1073/pnas.93.6.2348 / Proc Nat Acad Sci by Boyce (1996)
10.1073/pnas.92.22.10099 / Proc Nat Acad Sci by Hofmann (1995)
10.1128/JVI.69.10.6158-6169.1995 / J Virol by Guidotti (1995)
10.1126/science.6248960 / Science by Knowles (1980)
Virus methods. Baculovirus Expression Vectors. New York: Oxford University Press, 1994;124-138. / Virus methods. Baculovirus Expression Vectors. by O'Reilly (1994)
Analysis and Cloning of Eukaryotic Genomic DNA. Molecular Cloning, 2nd Edition, eds Cold Spring Harbor: Cold Spring Harbor Laboratory Press, 1989;9.1-9.62. / Analysis and Cloning of Eukaryotic Genomic DNA. Molecular Cloning by Sambrook (1989)
Lactate Dehydrogenase. In: Bergmeyer J, Grabl M, eds. Methods in Enzymatic Analysis, 1983;118-125. by Vassault (1983)
10.1016/0003-2697(87)90021-2 / Anal Biochem by Chomczynski (1987)
Preparation and Analysis of RNA from Eukaryotic Cells. Basic Methods in Molecular Biology, New York: Elsevier Science Publishing Co., Inc. 1986;129-156. / Preparation and Analysis of RNA from Eukaryotic Cells. Basic Methods in Molecular Biology by Davis (1986)
10.1016/0042-6822(88)90062-1 / Virology by Hirsch (1988)
10.1128/JVI.64.6.2819-2824.1990 / J Virol by Summers (1990)
10.1128/JVI.70.9.6455-6458.1996 / J Virol by Wei (1996)
10.1128/JVI.62.8.2836-2844.1988 / J Virol by Sells (1988)
10.1002/jmv.1890010205 / J Med Virol by Hruska (1977)
10.4049/jimmunol.117.4.1392 / J Immunol by Takahashi (1976)
10.1128/JVI.10.3.469-476.1972 / J Virol by Dreesman (1972)
10.1128/AAC.41.7.1444 / Antimicro Agents Chemo by Innaimo (1997)
10.1016/S0006-2952(97)82446-X / Biochem Pharm by Hostetler (1997)
10.1073/pnas.88.19.8495 / Proc Nat Acad Sci by Doong (1991)
10.1093/infdis/164.5.843 / J Infect Dis by Aoki-Sei (1991)
10.1016/0166-3542(92)90056-B / Antiviral Res by Korba (1992)
10.1128/AAC.38.9.2180 / Antimicro Agents Chemo by Heijtink (1994)
10.1128/AAC.38.9.2172 / Antimicro Agents Chemo by Schinazi (1994)
10.1046/j.1365-2362.1996.410595.x / Eur J Clin Invest by Lee (1996)
10.1099/0022-1317-78-6-1463 / J Gen Virol by Ling (1997)
10.1007/s007050050158 / Arch Virol by Moriyama (1997)
10.1074/jbc.272.27.16934 / J Biol Chem by Choi (1997)
10.1074/jbc.272.11.7132 / J Biol Chem by Lin (1997)
10.1128/JVI.70.12.8719-8726.1996 / J Virol by Yu (1996)
10.1006/viro.1996.0655 / Virology by Moriyama (1996)
10.1099/0022-1317-78-6-1479 / J Gen Virol by Moriyama (1997)
10.1002/hep.510230103 / Hepatology by Romero (1996)
10.1128/JVI.71.1.345-353.1997 / J Virol by Scaglioni (1997)
10.1128/JVI.71.11.8448-8455.1997 / J Virol by Perri (1997)
Hepatitis B Virus. In: eds. Fields Virology. Ed. 3. Philadelphia: Lippincott-Raven, 1996;2738-2808. / Fields Virology. by Hollinger (1996)
10.1073/pnas.86.1.207 / Proc Nat Acad Sci by Araki (1989)
10.1128/MCB.7.8.2745 / Mol Cell Biol by Chen (1987)
10.1111/j.1365-2893.1997.tb00162.x / J Vir Hepat by Hiramatsu (1997)
10.1006/abio.1997.2025 / Anal Biochem by Ourlin (1997)

Dates

Type	When
Created	21 years, 4 months ago (April 13, 2004, 6:37 a.m.)
Deposited	9 months ago (Dec. 1, 2024, 6:24 a.m.)
Indexed	1 month ago (July 30, 2025, 11:24 a.m.)
Issued	26 years, 11 months ago (Oct. 1, 1998)
Published	26 years, 11 months ago (Oct. 1, 1998)
Published Print	26 years, 11 months ago (Oct. 1, 1998)

Funders 0

None

BibTeX

@article{Delaney_1998, title={Hepatitis B virus replication in human HepG2 cells mediated by hepatitis B virus recombinant baculovirus}, volume={28}, ISSN={0270-9139}, url={http://dx.doi.org/10.1002/hep.510280432}, DOI={10.1002/hep.510280432}, number={4}, journal={Hepatology}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Delaney, William E. and Isom, Harriet C.}, year={1998}, month=oct, pages={1134–1146} }

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      "key": "BIB3",
      "first-page": "51",
      "volume": "55",
      "author": "Tyler",
      "year": "1986",
      "journal-title": "Lab Invest"
    },
    {
      "key": "BIB4",
      "doi-asserted-by": "crossref",
      "first-page": "323",
      "DOI": "10.1002/jmv.1890150402",
      "volume": "15",
      "author": "Sprengel",
      "year": "1985",
      "journal-title": "J Med Virol"
    },
    {
      "key": "BIB5",
      "doi-asserted-by": "crossref",
      "first-page": "25",
      "DOI": "10.1006/viro.1996.8422",
      "volume": "229",
      "author": "Di",
      "year": "1997",
      "journal-title": "Virology"
    },
    {
      "key": "BIB6",
      "doi-asserted-by": "crossref",
      "first-page": "1005",
      "DOI": "10.1073/pnas.84.4.1005",
      "volume": "84",
      "author": "Sells",
      "year": "1987",
      "journal-title": "Proc Nat Acad Sci"
    },
    {
      "key": "BIB7",
      "doi-asserted-by": "crossref",
      "first-page": "444",
      "DOI": "10.1073/pnas.84.2.444",
      "volume": "84",
      "author": "Tsurimoto",
      "year": "1987",
      "journal-title": "Proc Nat Acad Sci"
    },
    {
      "key": "BIB8",
      "doi-asserted-by": "crossref",
      "first-page": "214",
      "DOI": "10.1006/viro.1996.0049",
      "volume": "216",
      "author": "Weiss",
      "year": "1996",
      "journal-title": "Virology"
    },
    {
      "key": "BIB9",
      "doi-asserted-by": "crossref",
      "first-page": "451",
      "DOI": "10.1016/0092-8674(86)90602-1",
      "volume": "47",
      "author": "Tuttleman",
      "year": "1986",
      "journal-title": "Cell"
    },
    {
      "key": "BIB10",
      "doi-asserted-by": "crossref",
      "first-page": "533",
      "DOI": "10.1038/286533a0",
      "volume": "286",
      "author": "Brechot",
      "year": "1980",
      "journal-title": "Nature"
    },
    {
      "key": "BIB11",
      "doi-asserted-by": "crossref",
      "first-page": "773",
      "DOI": "10.1101/gad.1.8.773",
      "volume": "1",
      "author": "Nagaya",
      "year": "1987",
      "journal-title": "Genes Devel"
    },
    {
      "key": "BIB12",
      "doi-asserted-by": "crossref",
      "first-page": "1",
      "DOI": "10.1159/000149278",
      "volume": "17",
      "author": "Matthews",
      "year": "1982",
      "journal-title": "Intervirology"
    },
    {
      "key": "BIB13",
      "doi-asserted-by": "crossref",
      "first-page": "399",
      "DOI": "10.1128/MCB.4.3.399",
      "volume": "4",
      "author": "Pennock",
      "year": "1984",
      "journal-title": "Mol Cell Biol"
    },
    {
      "key": "BIB14",
      "doi-asserted-by": "crossref",
      "first-page": "69",
      "DOI": "10.1146/annurev.mi.45.100191.000441",
      "volume": "45",
      "author": "Wood",
      "year": "1991",
      "journal-title": "Ann Rev Micro"
    },
    {
      "key": "BIB15",
      "doi-asserted-by": "crossref",
      "first-page": "1937",
      "DOI": "10.1089/hum.1996.7.16-1937",
      "volume": "7",
      "author": "Sandig",
      "year": "1996",
      "journal-title": "Hum Gene Ther"
    },
    {
      "key": "BIB16",
      "doi-asserted-by": "crossref",
      "first-page": "2348",
      "DOI": "10.1073/pnas.93.6.2348",
      "volume": "93",
      "author": "Boyce",
      "year": "1996",
      "journal-title": "Proc Nat Acad Sci"
    },
    {
      "key": "BIB17",
      "doi-asserted-by": "crossref",
      "first-page": "10099",
      "DOI": "10.1073/pnas.92.22.10099",
      "volume": "92",
      "author": "Hofmann",
      "year": "1995",
      "journal-title": "Proc Nat Acad Sci"
    },
    {
      "key": "BIB18",
      "doi-asserted-by": "crossref",
      "first-page": "6158",
      "DOI": "10.1128/JVI.69.10.6158-6169.1995",
      "volume": "69",
      "author": "Guidotti",
      "year": "1995",
      "journal-title": "J Virol"
    },
    {
      "key": "BIB19",
      "doi-asserted-by": "crossref",
      "first-page": "497",
      "DOI": "10.1126/science.6248960",
      "volume": "209",
      "author": "Knowles",
      "year": "1980",
      "journal-title": "Science"
    },
    {
      "key": "BIB20",
      "first-page": "124",
      "volume-title": "Virus methods. Baculovirus Expression Vectors.",
      "author": "O'Reilly",
      "year": "1994",
      "unstructured": "Virus methods. Baculovirus Expression Vectors. New York: Oxford University Press, 1994;124-138."
    },
    {
      "key": "BIB21",
      "first-page": "9",
      "volume-title": "Analysis and Cloning of Eukaryotic Genomic DNA. Molecular Cloning",
      "author": "Sambrook",
      "year": "1989",
      "unstructured": "Analysis and Cloning of Eukaryotic Genomic DNA. Molecular Cloning, 2nd Edition, eds Cold Spring Harbor: Cold Spring Harbor Laboratory Press, 1989;9.1-9.62."
    },
    {
      "year": "1983",
      "author": "Vassault",
      "key": "BIB22",
      "unstructured": "Lactate Dehydrogenase. In: Bergmeyer J, Grabl M, eds. Methods in Enzymatic Analysis, 1983;118-125."
    },
    {
      "key": "BIB23",
      "doi-asserted-by": "crossref",
      "first-page": "156",
      "DOI": "10.1016/0003-2697(87)90021-2",
      "volume": "162",
      "author": "Chomczynski",
      "year": "1987",
      "journal-title": "Anal Biochem"
    },
    {
      "key": "BIB24",
      "first-page": "129",
      "volume-title": "Preparation and Analysis of RNA from Eukaryotic Cells. Basic Methods in Molecular Biology",
      "author": "Davis",
      "year": "1986",
      "unstructured": "Preparation and Analysis of RNA from Eukaryotic Cells. Basic Methods in Molecular Biology, New York: Elsevier Science Publishing Co., Inc. 1986;129-156."
    },
    {
      "key": "BIB25",
      "doi-asserted-by": "crossref",
      "first-page": "136",
      "DOI": "10.1016/0042-6822(88)90062-1",
      "volume": "167",
      "author": "Hirsch",
      "year": "1988",
      "journal-title": "Virology"
    },
    {
      "key": "BIB26",
      "doi-asserted-by": "crossref",
      "first-page": "2819",
      "DOI": "10.1128/JVI.64.6.2819-2824.1990",
      "volume": "64",
      "author": "Summers",
      "year": "1990",
      "journal-title": "J Virol"
    },
    {
      "key": "BIB27",
      "doi-asserted-by": "crossref",
      "first-page": "6455",
      "DOI": "10.1128/JVI.70.9.6455-6458.1996",
      "volume": "70",
      "author": "Wei",
      "year": "1996",
      "journal-title": "J Virol"
    },
    {
      "key": "BIB28",
      "doi-asserted-by": "crossref",
      "first-page": "2836",
      "DOI": "10.1128/JVI.62.8.2836-2844.1988",
      "volume": "62",
      "author": "Sells",
      "year": "1988",
      "journal-title": "J Virol"
    },
    {
      "key": "BIB29",
      "doi-asserted-by": "crossref",
      "first-page": "119",
      "DOI": "10.1002/jmv.1890010205",
      "volume": "1",
      "author": "Hruska",
      "year": "1977",
      "journal-title": "J Med Virol"
    },
    {
      "key": "BIB30",
      "doi-asserted-by": "crossref",
      "first-page": "1392",
      "DOI": "10.4049/jimmunol.117.4.1392",
      "volume": "117",
      "author": "Takahashi",
      "year": "1976",
      "journal-title": "J Immunol"
    },
    {
      "key": "BIB31",
      "doi-asserted-by": "crossref",
      "first-page": "469",
      "DOI": "10.1128/JVI.10.3.469-476.1972",
      "volume": "10",
      "author": "Dreesman",
      "year": "1972",
      "journal-title": "J Virol"
    },
    {
      "key": "BIB32",
      "doi-asserted-by": "crossref",
      "first-page": "1444",
      "DOI": "10.1128/AAC.41.7.1444",
      "volume": "41",
      "author": "Innaimo",
      "year": "1997",
      "journal-title": "Antimicro Agents Chemo"
    },
    {
      "key": "BIB33",
      "doi-asserted-by": "crossref",
      "first-page": "1815",
      "DOI": "10.1016/S0006-2952(97)82446-X",
      "volume": "53",
      "author": "Hostetler",
      "year": "1997",
      "journal-title": "Biochem Pharm"
    },
    {
      "key": "BIB34",
      "doi-asserted-by": "crossref",
      "first-page": "8495",
      "DOI": "10.1073/pnas.88.19.8495",
      "volume": "88",
      "author": "Doong",
      "year": "1991",
      "journal-title": "Proc Nat Acad Sci"
    },
    {
      "key": "BIB35",
      "doi-asserted-by": "crossref",
      "first-page": "843",
      "DOI": "10.1093/infdis/164.5.843",
      "volume": "164",
      "author": "Aoki-Sei",
      "year": "1991",
      "journal-title": "J Infect Dis"
    },
    {
      "key": "BIB36",
      "doi-asserted-by": "crossref",
      "first-page": "55",
      "DOI": "10.1016/0166-3542(92)90056-B",
      "volume": "19",
      "author": "Korba",
      "year": "1992",
      "journal-title": "Antiviral Res"
    },
    {
      "key": "BIB37",
      "doi-asserted-by": "crossref",
      "first-page": "2180",
      "DOI": "10.1128/AAC.38.9.2180",
      "volume": "38",
      "author": "Heijtink",
      "year": "1994",
      "journal-title": "Antimicro Agents Chemo"
    },
    {
      "key": "BIB38",
      "doi-asserted-by": "crossref",
      "first-page": "2172",
      "DOI": "10.1128/AAC.38.9.2172",
      "volume": "38",
      "author": "Schinazi",
      "year": "1994",
      "journal-title": "Antimicro Agents Chemo"
    },
    {
      "key": "BIB39",
      "doi-asserted-by": "crossref",
      "first-page": "1069",
      "DOI": "10.1046/j.1365-2362.1996.410595.x",
      "volume": "26",
      "author": "Lee",
      "year": "1996",
      "journal-title": "Eur J Clin Invest"
    },
    {
      "key": "BIB40",
      "doi-asserted-by": "crossref",
      "first-page": "1463",
      "DOI": "10.1099/0022-1317-78-6-1463",
      "volume": "78",
      "author": "Ling",
      "year": "1997",
      "journal-title": "J Gen Virol"
    },
    {
      "key": "BIB41",
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      "first-page": "1263",
      "DOI": "10.1007/s007050050158",
      "volume": "142",
      "author": "Moriyama",
      "year": "1997",
      "journal-title": "Arch Virol"
    },
    {
      "key": "BIB42",
      "doi-asserted-by": "crossref",
      "first-page": "16934",
      "DOI": "10.1074/jbc.272.27.16934",
      "volume": "272",
      "author": "Choi",
      "year": "1997",
      "journal-title": "J Biol Chem"
    },
    {
      "key": "BIB43",
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      "year": "1996",
      "journal-title": "J Virol"
    },
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      "first-page": "269",
      "DOI": "10.1006/viro.1996.0655",
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      "author": "Moriyama",
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      "DOI": "10.1099/0022-1317-78-6-1479",
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      "year": "1997",
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      "DOI": "10.1002/hep.510230103",
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      "journal-title": "Hepatology"
    },
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      "DOI": "10.1006/abio.1997.2025",
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