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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1988 Dec;85(24):9792–9796. doi: 10.1073/pnas.85.24.9792

Maternal transmission of retroviral disease: transgenic mice as a rapid test system for evaluating perinatal and transplacental antiretroviral therapy.

A H Sharpe 1, J J Hunter 1, R M Ruprecht 1, R Jaenisch 1
PMCID: PMC282867  PMID: 2849117

Abstract

Transgenic mouse strains carrying Moloney murine leukemia virus (Mo-MuLV) in the germ line were found to serve as rapid and quantitative models of in utero and perinatal retroviral infection for evaluating strategies of antiretroviral therapy. In these strains virus activation leads to virus expression, viral spread associated with the development of viremia, and subsequent T-cell leukemia/lymphoma. To test these transgenic strains for their usefulness in evaluating antiretroviral agents, the effect of the drug 3'-azido-3'-deoxythymidine (AZT) on the development of viremia and subsequent disease was examined. The assessment of mice for viremia at 1 month of age appeared to be the most useful assay because it was rapid and quantitative. AZT was most effective in preventing viremia in transgenic strains that activate Mo-MuLV after birth and had more variable effects in strains that activate prior to birth. However, in six of seven of the strains examined, AZT led to a marked improvement in survival and reduced the onset of T-cell leukemia/lymphoma. These results provide evidence for effective antiretroviral therapy during gestation and in the perinatal period and are of potential significance for the management of the maternal transmission of human retroviruses.

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Selected References

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

  1. Ando Y., Nakano S., Saito K., Shimamoto I., Ichijo M., Toyama T., Hinuma Y. Transmission of adult T-cell leukemia retrovirus (HTLV-I) from mother to child: comparison of bottle- with breast-fed babies. Jpn J Cancer Res. 1987 Apr;78(4):322–324. [PubMed] [Google Scholar]
  2. Berleth T., Nobis P., Jaenisch R., Harbers K. Activation of endogenous retroviral genomes in Mov strains of mice. J Gen Virol. 1987 Nov;68(Pt 11):2919–2923. doi: 10.1099/0022-1317-68-11-2919. [DOI] [PubMed] [Google Scholar]
  3. Buffett R. F., Grace J. T., Jr, DiBerardino L. A., Mirand E. A. Vertical transmission of murine leukemia virus. Cancer Res. 1969 Mar;29(3):588–595. [PubMed] [Google Scholar]
  4. Friedland G. H., Klein R. S. Transmission of the human immunodeficiency virus. N Engl J Med. 1987 Oct 29;317(18):1125–1135. doi: 10.1056/NEJM198710293171806. [DOI] [PubMed] [Google Scholar]
  5. Ida N., Fukuhara A., Ohba Y. Several aspects of vertical transmission of Moloney virus. Natl Cancer Inst Monogr. 1966 Sep;22:287–311. [PubMed] [Google Scholar]
  6. Jaenisch R. Germ line integration and Mendelian transmission of the exogenous Moloney leukemia virus. Proc Natl Acad Sci U S A. 1976 Apr;73(4):1260–1264. doi: 10.1073/pnas.73.4.1260. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Jaenisch R., Jähner D., Nobis P., Simon I., Löhler J., Harbers K., Grotkopp D. Chromosomal position and activation of retroviral genomes inserted into the germ line of mice. Cell. 1981 May;24(2):519–529. doi: 10.1016/0092-8674(81)90343-3. [DOI] [PubMed] [Google Scholar]
  8. Jaenisch R. Retroviruses and embryogenesis: microinjection of Moloney leukemia virus into midgestation mouse embryos. Cell. 1980 Jan;19(1):181–188. doi: 10.1016/0092-8674(80)90399-2. [DOI] [PubMed] [Google Scholar]
  9. Jähner D., Jaenisch R. Integration of Moloney leukaemia virus into the germ line of mice: correlation between site of integration and virus activation. Nature. 1980 Oct 2;287(5781):456–458. doi: 10.1038/287456a0. [DOI] [PubMed] [Google Scholar]
  10. Law L. W. Transmission studies of a leukemogenic virus, MLV, in mice. Natl Cancer Inst Monogr. 1966 Sep;22:267–285. [PubMed] [Google Scholar]
  11. Lepage P., Van de Perre P., Caraël M., Nsengumuremyi F., Nkurunziza J., Butzler J. P., Sprecher S. Postnatal transmission of HIV from mother to child. Lancet. 1987 Aug 15;2(8555):400–400. doi: 10.1016/s0140-6736(87)92423-8. [DOI] [PubMed] [Google Scholar]
  12. Lifson A. R. Do alternate modes for transmission of human immunodeficiency virus exist? A review. JAMA. 1988 Mar 4;259(9):1353–1356. [PubMed] [Google Scholar]
  13. Lin T. S., Prusoff W. H. Synthesis and biological activity of several amino analogues of thymidine. J Med Chem. 1978 Jan;21(1):109–112. [PubMed] [Google Scholar]
  14. Mitsuya H., Weinhold K. J., Furman P. A., St Clair M. H., Lehrman S. N., Gallo R. C., Bolognesi D., Barry D. W., Broder S. 3'-Azido-3'-deoxythymidine (BW A509U): an antiviral agent that inhibits the infectivity and cytopathic effect of human T-lymphotropic virus type III/lymphadenopathy-associated virus in vitro. Proc Natl Acad Sci U S A. 1985 Oct;82(20):7096–7100. doi: 10.1073/pnas.82.20.7096. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Nakano S., Ando Y., Saito K., Moriyama I., Ichijo M., Toyama T., Sugamura K., Imai J., Hinuma Y. Primary infection of Japanese infants with adult T-cell leukaemia-associated retrovirus (ATLV): evidence for viral transmission from mothers to children. J Infect. 1986 May;12(3):205–212. doi: 10.1016/s0163-4453(86)94086-7. [DOI] [PubMed] [Google Scholar]
  16. Nobis P., Jaenisch R. Passive immunotherapy prevents expression of endogenous Moloney virus and amplification of proviral DNA in BALB/Mo mice. Proc Natl Acad Sci U S A. 1980 Jun;77(6):3677–3681. doi: 10.1073/pnas.77.6.3677. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Rowe W. P., Pugh W. E., Hartley J. W. Plaque assay techniques for murine leukemia viruses. Virology. 1970 Dec;42(4):1136–1139. doi: 10.1016/0042-6822(70)90362-4. [DOI] [PubMed] [Google Scholar]
  18. Ruprecht R. M., O'Brien L. G., Rossoni L. D., Nusinoff-Lehrman S. Suppression of mouse viraemia and retroviral disease by 3'-azido-3'-deoxythymidine. Nature. 1986 Oct 2;323(6087):467–469. doi: 10.1038/323467a0. [DOI] [PubMed] [Google Scholar]
  19. Sharpe A. H., Jaenisch R., Ruprecht R. M. Retroviruses and mouse embryos: a rapid model for neurovirulence and transplacental antiviral therapy. Science. 1987 Jun 26;236(4809):1671–1674. doi: 10.1126/science.3037694. [DOI] [PubMed] [Google Scholar]
  20. Soriano P., Jaenisch R. Retroviruses as probes for mammalian development: allocation of cells to the somatic and germ cell lineages. Cell. 1986 Jul 4;46(1):19–29. doi: 10.1016/0092-8674(86)90856-1. [DOI] [PubMed] [Google Scholar]
  21. Stewart C., Harbers K., Jähner D., Jaenisch R. X chromosome-linked transmission and expression of retroviral genomes microinjected into mouse zygotes. Science. 1983 Aug 19;221(4612):760–762. doi: 10.1126/science.6683871. [DOI] [PubMed] [Google Scholar]
  22. Thiry L., Sprecher-Goldberger S., Jonckheer T., Levy J., Van de Perre P., Henrivaux P., Cogniaux-LeClerc J., Clumeck N. Isolation of AIDS virus from cell-free breast milk of three healthy virus carriers. Lancet. 1985 Oct 19;2(8460):891–892. doi: 10.1016/s0140-6736(85)90156-4. [DOI] [PubMed] [Google Scholar]

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