Skip to main content
PMC home page
Journal of Virology logoLink to Journal of Virology
. 1986 Apr;58(1):1–8. doi: 10.1128/jvi.58.1.1-8.1986

Hepadnavirus infection of peripheral blood lymphocytes in vivo: woodchuck and chimpanzee models of viral hepatitis.

B E Korba, F Wells, B C Tennant, G H Yoakum, R H Purcell, J L Gerin
PMCID: PMC252868  PMID: 3485201

Abstract

The peripheral blood lymphocytes (PBL) of five hepatitis B virus (HBV)-infected chimpanzees and 17 woodchuck hepatitis virus (WHV)-infected woodchucks were examined for the presence of viral DNA and RNA. HBV DNA was detected in the PBL of three of three chronically infected chimpanzees but in neither of two animals with acute HBV infection. WHV DNA was found in the PBL of 11 of 13 chronically infected woodchucks and in the PBL and bone marrow of 1 of 4 woodchucks with antibody to WHV surface antigen. Viral DNA in the PBL and bone marrow was episomal, primarily existing as multimers with some monomeric forms. Integrated HBV DNA was detected in the PBL of one chronically infected chimpanzee, but only for a brief period. Viral RNA was also detected in the PBL, although less frequently than was DNA. HBV RNA in chimpanzee PBL existed as 3.8- and 7.5-kilobase species, while 2.3- and 3.8-kilobase WHV RNA was found in woodchuck PBL. Subfractionation of PBL isolated from the chronically infected chimpanzees demonstrated that HBV DNA and RNA were located in B and T cells. No HBV DNA was detected in the macrophages. These results, along with the recent reports of HBV nucleic acids in the PBL of human patients, suggest that infection of PBL may be a general phenomenon associated with the pathology of hepadnaviruses.

Full text

PDF
1

Images in this article

4Image
on p.4
4Image
on p.4
5Image
on p.5
5Image
on p.5
6Image
on p.6

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Barker L. F., Maynard J. E., Purcell R. H., Hoofnagle J. H., Berquist K. R., London W. T. Viral hepatitis, type B, in experimental animals. Am J Med Sci. 1975 Jul-Aug;270(1):189–195. doi: 10.1097/00000441-197507000-00026. [DOI] [PubMed] [Google Scholar]
  2. Blum H. E., Stowring L., Figus A., Montgomery C. K., Haase A. T., Vyas G. N. Detection of hepatitis B virus DNA in hepatocytes, bile duct epithelium, and vascular elements by in situ hybridization. Proc Natl Acad Sci U S A. 1983 Nov;80(21):6685–6688. doi: 10.1073/pnas.80.21.6685. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cote P. J., Jr, Dapolito G. M., Shih J. W., Gerin J. L. Surface antigenic determinants of mammalian "hepadnaviruses" defined by group- and class-specific monoclonal antibodies. J Virol. 1982 Apr;42(1):135–142. doi: 10.1128/jvi.42.1.135-142.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Elfassi E., Romet-Lemonne J. L., Essex M., Frances-McLane M., Haseltine W. A. Evidence of extrachromosomal forms of hepatitis B viral DNA in a bone marrow culture obtained from a patient recently infected with hepatitis B virus. Proc Natl Acad Sci U S A. 1984 Jun;81(11):3526–3528. doi: 10.1073/pnas.81.11.3526. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Feinman S. V., Overby L. R., Berris B., Chau K., Schable C. A., Maynard J. E. The significance of IgM antibodies to hepatitis B core antigen in hepatitis B carriers and hepatitis B-associated chronic liver disease. Hepatology. 1982 Nov-Dec;2(6):795–799. doi: 10.1002/hep.1840020609. [DOI] [PubMed] [Google Scholar]
  6. Galibert F., Chen T. N., Mandart E. Nucleotide sequence of a cloned woodchuck hepatitis virus genome: comparison with the hepatitis B virus sequence. J Virol. 1982 Jan;41(1):51–65. doi: 10.1128/jvi.41.1.51-65.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Galibert F., Mandart E., Fitoussi F., Tiollais P., Charnay P. Nucleotide sequence of the hepatitis B virus genome (subtype ayw) cloned in E. coli. Nature. 1979 Oct 25;281(5733):646–650. doi: 10.1038/281646a0. [DOI] [PubMed] [Google Scholar]
  8. Halpern M. S., England J. M., Deery D. T., Petcu D. J., Mason W. S., Molnar-Kimber K. L. Viral nucleic acid synthesis and antigen accumulation in pancreas and kidney of Pekin ducks infected with duck hepatitis B virus. Proc Natl Acad Sci U S A. 1983 Aug;80(15):4865–4869. doi: 10.1073/pnas.80.15.4865. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Harris C. C., Sun T. Multifactoral etiology of human liver cancer. Carcinogenesis. 1984 Jun;5(6):697–701. doi: 10.1093/carcin/5.6.697. [DOI] [PubMed] [Google Scholar]
  10. Korba B. E., Wilson V. L., Yoakum G. H. Induction of hepatitis B virus core gene in human cells by cytosine demethylation in the promoter. Science. 1985 May 31;228(4703):1103–1106. doi: 10.1126/science.2581318. [DOI] [PubMed] [Google Scholar]
  11. Laure F., Zagury D., Saimot A. G., Gallo R. C., Hahn B. H., Brechot C. Hepatitis B virus DNA sequences in lymphoid cells from patients with AIDS and AIDS-related complex. Science. 1985 Aug 9;229(4713):561–563. doi: 10.1126/science.2410981. [DOI] [PubMed] [Google Scholar]
  12. Lie-Injo L. E., Balasegaram M., Lopez C. G., Herrera A. R. Hepatitis B virus DNA in liver and white blood cells of patients with hepatoma. DNA. 1983;2(4):301–308. doi: 10.1089/dna.1983.2.301. [DOI] [PubMed] [Google Scholar]
  13. Mason W. S., Aldrich C., Summers J., Taylor J. M. Asymmetric replication of duck hepatitis B virus DNA in liver cells: Free minus-strand DNA. Proc Natl Acad Sci U S A. 1982 Jul;79(13):3997–4001. doi: 10.1073/pnas.79.13.3997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Overby L. R., Hung P. P., Mao J. C., Ling C. M. Rolling circular DNA associated with Dane particles in hepatitis B virus. Nature. 1975 May 1;255(5503):84–85. doi: 10.1038/255084a0. [DOI] [PubMed] [Google Scholar]
  15. Patterson M., Gonzalez-Vitale J. C., Fagan C. J. Polycystic liver disease: a study of cyst fluid constituents. Hepatology. 1982 Jul-Aug;2(4):475–478. doi: 10.1002/hep.1840020414. [DOI] [PubMed] [Google Scholar]
  16. Pontisso P., Poon M. C., Tiollais P., Brechot C. Detection of hepatitis B virus DNA in mononuclear blood cells. Br Med J (Clin Res Ed) 1984 May 26;288(6430):1563–1566. doi: 10.1136/bmj.288.6430.1563. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Ponzetto A., Cote P. J., Ford E. C., Engle R., Cicmanec J., Shapiro M., Purcell R. H., Gerin J. L. Radioimmunoassay and characterization of woodchuck hepatitis virus core antigen and antibody. Virus Res. 1985 Jun;2(4):301–315. doi: 10.1016/0168-1702(85)90027-9. [DOI] [PubMed] [Google Scholar]
  18. Popper H., Shih J. W., Gerin J. L., Wong D. C., Hoyer B. H., London W. T., Sly D. L., Purcell R. H. Woodchuck hepatitis and hepatocellular carcinoma: correlation of histologic with virologic observations. Hepatology. 1981 Mar-Apr;1(2):91–98. doi: 10.1002/hep.1840010202. [DOI] [PubMed] [Google Scholar]
  19. Rave N., Crkvenjakov R., Boedtker H. Identification of procollagen mRNAs transferred to diazobenzyloxymethyl paper from formaldehyde agarose gels. Nucleic Acids Res. 1979 Aug 10;6(11):3559–3567. doi: 10.1093/nar/6.11.3559. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Rizzetto M., Hoyer B., Canese M. G., Shih J. W., Purcell R. H., Gerin J. L. delta Agent: association of delta antigen with hepatitis B surface antigen and RNA in serum of delta-infected chimpanzees. Proc Natl Acad Sci U S A. 1980 Oct;77(10):6124–6128. doi: 10.1073/pnas.77.10.6124. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Rogler C. E., Summers J. Novel forms of woodchuck hepatitis virus DNA isolated from chronically infected woodchuck liver nuclei. J Virol. 1982 Dec;44(3):852–863. doi: 10.1128/jvi.44.3.852-863.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Romet-Lemonne J. L., Elfassi E., Haseltine W., Essex M. Infection of bone marrow cells by hepatitis B virus. Lancet. 1983 Sep 24;2(8352):732–732. doi: 10.1016/s0140-6736(83)92264-x. [DOI] [PubMed] [Google Scholar]
  23. Romet-Lemonne J. L., McLane M. F., Elfassi E., Haseltine W. A., Azocar J., Essex M. Hepatitis B virus infection in cultured human lymphoblastoid cells. Science. 1983 Aug 12;221(4611):667–669. doi: 10.1126/science.6867736. [DOI] [PubMed] [Google Scholar]
  24. Schweizer J., Goerttler K. Synthesis in vitro of keratin polypeptides directed by mRNA isolated from newborn and adult mouse epidermis. Eur J Biochem. 1980 Nov;112(2):243–249. doi: 10.1111/j.1432-1033.1980.tb07200.x. [DOI] [PubMed] [Google Scholar]
  25. Siddiqui A. Hepatitis B virus DNA in Kaposi sarcoma. Proc Natl Acad Sci U S A. 1983 Aug;80(15):4861–4864. doi: 10.1073/pnas.80.15.4861. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  27. Summers J., Mason W. S. Replication of the genome of a hepatitis B--like virus by reverse transcription of an RNA intermediate. Cell. 1982 Jun;29(2):403–415. doi: 10.1016/0092-8674(82)90157-x. [DOI] [PubMed] [Google Scholar]
  28. Summers J., Smolec J. M., Snyder R. A virus similar to human hepatitis B virus associated with hepatitis and hepatoma in woodchucks. Proc Natl Acad Sci U S A. 1978 Sep;75(9):4533–4537. doi: 10.1073/pnas.75.9.4533. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Wahl G. M., Stern M., Stark G. R. Efficient transfer of large DNA fragments from agarose gels to diazobenzyloxymethyl-paper and rapid hybridization by using dextran sulfate. Proc Natl Acad Sci U S A. 1979 Aug;76(8):3683–3687. doi: 10.1073/pnas.76.8.3683. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Yoakum G. H., Korba B. E., Lechner J. F., Tokiwa T., Gazdar A. F., Seeley T., Siegel M., Leeman L., Autrup H., Harris C. C. High-frequency transfection and cytopathology of the hepatitis B virus core antigen gene in human cells. Science. 1983 Oct 28;222(4622):385–389. doi: 10.1126/science.6194563. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES