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Use of In vivo Imaging to Monitor the Progression of Experimental Mouse Cytomegalovirus Infection in Neonates
Published on: July 6, 2013
Prenatal transmission and pathogenicity of endogenous ecotropic murine leukemia virus Akv
1Institute of Molecular Virology, GSF-National Research Center for Environment and Health, Neuherberg, Germany.
Objective:
Mouse strains carrying endogenous ecotropic murine leukemia viruses (MuLV) are capable of expressing infective virus throughout life. Risk of transplacental transmission of MuLV raises concerns of embryo infection and induction of pathogenic effects, and postnatal MuLV infection may lead to tumorigenesis.
Methods:
Endogenous ecotropic MuLV-negative SWR/J embryos were implanted into Akv-infected viremic SWR/J mice, into spontaneously provirus-expressing AKR/J mice, and into noninfected SWR/J control mice; virus integration and virus expression were investigated at 14 days' gestation. Tumor development was monitored over 18 months.
Results:
Of 111 embryos, 20 (18%) recovered from Akv-infected SWR/J mice, which had developed normally, were infected. New proviruses were detected in 10 of 111 (9%) embryos from Akv-infected SWR/J mice, and in 2 of 60 (3%) embryos from AKR/J mice; none expressed viral protein. Of 127 embryos recovered from Akv-infected SWR/J mice, 16 (13%) were dead; 4 of 5 (80%) were infected and expressed viral protein. Of 71 embryos from AKR/J mice, 11 (15%) were dead, and 2 of 2 had virus integration; virus expression was not detected. Numbers of dead embryos recovered from experimentally infected, viremic SWR/J mice and from spontaneously endogenous MuLV-expressing AKR/J mice were significantly higher, compared with numbers from nonviremic SWR/J control mice, and embryo lethality was significantly associated with prenatal provirus expression. Postnatal inoculation of Akv induced lymphoblastic lymphomas in 15 of 24 (61%) SWR/J mice within mean +/- SD latency of 14 +/- 2.4 months. Only 3 of 39 (8%) control mice developed lymphomas (P < 0.005).
Conclusion:
Embryos in MuLV-viremic dams are readily infected, and inappropriate prenatal expression of leukemogenic endogenous retroviruses may play a critical role in embryo lethality and decreased breeding performance in ecotropic provirus-positive mouse strains.
Insights
Prenatal exposure to murine leukemia viruses (MuLV) in dams readily infects embryos, leading to increased embryo lethality. Inappropriate expression of these endogenous retroviruses during gestation is linked to embryo death and reduced breeding success in mice.
Area of Science:
- Virology
- Immunology
- Developmental Biology
Background:
- Endogenous ecotropic murine leukemia viruses (MuLV) can be expressed throughout life in mice.
- Transplacental transmission of MuLV poses risks of embryo infection and pathogenic effects.
- Postnatal MuLV infection is associated with tumorigenesis.
Purpose of the Study:
- To investigate the impact of maternal MuLV viremia on embryonic development and survival.
- To determine the role of prenatal MuLV infection and expression in embryo lethality.
- To assess the long-term effects of MuLV infection on tumor development in mice.
Main Methods:
- Implantation of MuLV-negative embryos into MuLV-infected or control dams.
- Analysis of virus integration and expression in embryos at 14 days' gestation.
- Monitoring of tumor development over 18 months post-birth.
Main Results:
- Embryos from MuLV-viremic dams showed higher infection rates and increased lethality, significantly associated with prenatal provirus expression.
- Prenatal MuLV infection and expression were linked to embryo death.
- Postnatal MuLV infection significantly increased the incidence of lymphoblastic lymphomas compared to controls.
Conclusions:
- Embryos gestated in MuLV-viremic dams are susceptible to infection.
- Inappropriate prenatal expression of endogenous retroviruses contributes to embryo lethality and impaired reproductive performance.
- MuLV infection is a significant risk factor for tumorigenesis in mice.

