Open AccessMaternal transmission of retroviral disease: transgenic mice as a rapid test system for evaluating perinatal and transplacental antiretroviral therapy.
Author(s) -
Arlene H. Sharpe,
John Hunter,
Ruth M. Ruprecht,
Rudolf Jaenisch
Publication year - 1988
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.85.24.9792
Subject(s) - viremia , virology , transplacental , zidovudine , biology , lymphoma , immunology , leukemia , transgene , virus , genetically modified mouse , viral disease , fetus , pregnancy , placenta , genetics , gene
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.