Skip to main content
NCBI home page
Journal of Virology logoLink to Journal of Virology
. 1990 Nov;64(11):5665–5668. doi: 10.1128/jvi.64.11.5665-5668.1990

Antibodies to the RNase H domain of hepatitis B virus P protein are associated with ongoing viral replication.

T Weimer 1, F Schödel 1, M C Jung 1, G R Pape 1, A Alberti 1, G Fattovich 1, H Beljaars 1, P M van Eerd 1, H Will 1
PMCID: PMC248626  PMID: 2170693

Abstract

Antibodies against the RNase H domain of human hepatitis B virus P protein(s) are frequent markers of acute and chronic virus infection (T. Weimer, K. Weimer, Z.-X. Tu, M.-C. Jung, G. R. Pape, and H. Will, J. Immunol. 143:3750-3756, 1989). In the present study, these antibodies were determined in serial serum samples of experimentally infected chimpanzees and naturally infected human patients with acute and chronic hepatitis B virus infection. Anti-P antibodies were found in the sera of both chimpanzees and humans early in infection shortly after the immunoglobulin M anti-HBc response; they persisted in chronic carriers with ongoing viral replication but declined and disappeared at the time of virus clearance from the sera. These data demonstrate that antibodies to the RNase H domain of the hepatitis B virus P protein are early markers of infection and a signal of ongoing virus replication. Falling titers indicate the decline or end of active virus production and may therefore be a prognostic sign of virus elimination in natural infection and after antiviral therapy.

Full text

PDF
5665

Images in this article

5665Image
on p.5665

Selected References

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

  1. Aaronson S. A., Parks W. P., Scolnick E. M., Todaro G. J. Antibody to the RNA-dependent DNA polymerase of mammalian C-type RNA tumor viruses. Proc Natl Acad Sci U S A. 1971 May;68(5):920–924. doi: 10.1073/pnas.68.5.920. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bartenschlager R., Schaller H. The amino-terminal domain of the hepadnaviral P-gene encodes the terminal protein (genome-linked protein) believed to prime reverse transcription. EMBO J. 1988 Dec 20;7(13):4185–4192. doi: 10.1002/j.1460-2075.1988.tb03315.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brunetto M. R., Stemler M., Bonino F., Schodel F., Oliveri F., Rizzetto M., Verme G., Will H. A new hepatitis B virus strain in patients with severe anti-HBe positive chronic hepatitis B. J Hepatol. 1990 Mar;10(2):258–261. doi: 10.1016/0168-8278(90)90062-v. [DOI] [PubMed] [Google Scholar]
  4. Carman W. F., Jacyna M. R., Hadziyannis S., Karayiannis P., McGarvey M. J., Makris A., Thomas H. C. Mutation preventing formation of hepatitis B e antigen in patients with chronic hepatitis B infection. Lancet. 1989 Sep 9;2(8663):588–591. doi: 10.1016/s0140-6736(89)90713-7. [DOI] [PubMed] [Google Scholar]
  5. Chang L. J., Dienstag J., Ganem D., Varmus H. Detection of antibodies against hepatitis B virus polymerase antigen in hepatitis B virus-infected patients. Hepatology. 1989 Sep;10(3):332–335. doi: 10.1002/hep.1840100314. [DOI] [PubMed] [Google Scholar]
  6. Desmet V. J. Liver lesions in hepatitis B viral infection. Yale J Biol Med. 1988 Jan-Feb;61(1):61–83. [PMC free article] [PubMed] [Google Scholar]
  7. Enders A. The influence of general, volatile anesthetics on the dynamic properties of model membranes. Biochim Biophys Acta. 1990 Nov 2;1029(1):43–50. doi: 10.1016/0005-2736(90)90434-p. [DOI] [PubMed] [Google Scholar]
  8. Feitelson M. A., Millman I., Duncan G. D., Blumberg B. S. Presence of antibodies to the polymerase gene product(s) of hepatitis B and woodchuck hepatitis virus in natural and experimental infections. J Med Virol. 1988 Feb;24(2):121–136. doi: 10.1002/jmv.1890240202. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. Hollis V. W., Jr, Aoki T., Barrera O., Oldstone M. B., Dixon F. J. Detection of naturally occurring antibodies to RNA-dependent DNA polymerase of murine leukemia virus in kidney eluates of AKR mice. J Virol. 1974 Feb;13(2):448–454. doi: 10.1128/jvi.13.2.448-454.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hoofnagle J. H., Shafritz D. A., Popper H. Chronic type B hepatitis and the "healthy" HBsAg carrier state. Hepatology. 1987 Jul-Aug;7(4):758–763. doi: 10.1002/hep.1840070424. [DOI] [PubMed] [Google Scholar]
  12. Jacquemin P. C., Saxinger C., Gallo R. C., Hardy W. D., Jr, Essex M. Antibody response in cats to feline leukemia virus reverse transcriptase under natural conditions of exposure to the virus. Virology. 1978 Dec;91(2):472–476. doi: 10.1016/0042-6822(78)90393-8. [DOI] [PubMed] [Google Scholar]
  13. Khudyakov YuE, Makhov A. M. Prediction of terminal protein and ribonuclease H domains in the gene P product of hepadnaviruses. FEBS Lett. 1989 Jan 30;243(2):115–118. doi: 10.1016/0014-5793(89)80110-3. [DOI] [PubMed] [Google Scholar]
  14. Klinkert M. Q., Theilmann L., Pfaff E., Schaller H. Pre-S1 antigens and antibodies early in the course of acute hepatitis B virus infection. J Virol. 1986 May;58(2):522–525. doi: 10.1128/jvi.58.2.522-525.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Laurence J., Saunders A., Kulkosky J. Characterization and clinical association of antibody inhibitory to HIV reverse transcriptase activity. Science. 1987 Mar 20;235(4795):1501–1504. doi: 10.1126/science.2435004. [DOI] [PubMed] [Google Scholar]
  16. Okamoto H., Yotsumoto S., Akahane Y., Yamanaka T., Miyazaki Y., Sugai Y., Tsuda F., Tanaka T., Miyakawa Y., Mayumi M. Hepatitis B viruses with precore region defects prevail in persistently infected hosts along with seroconversion to the antibody against e antigen. J Virol. 1990 Mar;64(3):1298–1303. doi: 10.1128/jvi.64.3.1298-1303.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Padberg C., Nowlan S., Mermer B. Recombinant polypeptides from the human immunodeficiency virus reverse transcriptase define three epitopes recognized by antibodies in sera from patients with acquired immunodeficiency syndrome. AIDS Res Hum Retroviruses. 1989 Feb;5(1):61–71. doi: 10.1089/aid.1989.5.61. [DOI] [PubMed] [Google Scholar]
  18. Radziwill G., Tucker W., Schaller H. Mutational analysis of the hepatitis B virus P gene product: domain structure and RNase H activity. J Virol. 1990 Feb;64(2):613–620. doi: 10.1128/jvi.64.2.613-620.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Stemler M., Hess J., Braun R., Will H., Schröder C. H. Serological evidence for expression of the polymerase gene of human hepatitis B virus in vivo. J Gen Virol. 1988 Mar;69(Pt 3):689–693. doi: 10.1099/0022-1317-69-3-689. [DOI] [PubMed] [Google Scholar]
  20. Toh H., Hayashida H., Miyata T. Sequence homology between retroviral reverse transcriptase and putative polymerases of hepatitis B virus and cauliflower mosaic virus. 1983 Oct 27-Nov 2Nature. 305(5937):827–829. doi: 10.1038/305827a0. [DOI] [PubMed] [Google Scholar]
  21. Weimer T., Weimer K., Tu Z. X., Jung M. C., Pape G. R., Will H. Immunogenicity of human hepatitis B virus P-gene derived proteins. J Immunol. 1989 Dec 1;143(11):3750–3756. [PubMed] [Google Scholar]
  22. Will H., Cattaneo R., Darai G., Deinhardt F., Schellekens H., Schaller H. Infectious hepatitis B virus from cloned DNA of known nucleotide sequence. Proc Natl Acad Sci U S A. 1985 Feb;82(3):891–895. doi: 10.1073/pnas.82.3.891. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Will H., Cattaneo R., Koch H. G., Darai G., Schaller H., Schellekens H., van Eerd P. M., Deinhardt F. Cloned HBV DNA causes hepatitis in chimpanzees. Nature. 1982 Oct 21;299(5885):740–742. doi: 10.1038/299740a0. [DOI] [PubMed] [Google Scholar]
  24. Wuu K. D., Graves D. C., Ferrer J. F. Inhibition of the reverse transcriptase of bovine leukemia virus by antibody in sera from leukemic cattle and immunological characterization of the enzyme. Cancer Res. 1977 May;37(5):1438–1442. [PubMed] [Google Scholar]
  25. di Marzo Veronese F., Copeland T. D., DeVico A. L., Rahman R., Oroszlan S., Gallo R. C., Sarngadharan M. G. Characterization of highly immunogenic p66/p51 as the reverse transcriptase of HTLV-III/LAV. Science. 1986 Mar 14;231(4743):1289–1291. doi: 10.1126/science.2418504. [DOI] [PubMed] [Google Scholar]

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

RESOURCES