Prenatal transmission and pathogenicity of endogenous ecotropic murine leukemia virus Akv

Objective: Mouse strains carrying endogenous ecotropic murine leukemia viru ses (MuLV) are capable of ex pressing 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 in to 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, w hich 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%) e mbryos from AKR/J mice; none expressed viral protein. Of 127 embryos recove red from Akv-infected SWR/J mice, 16 (13%) were dead; 4 of 5 (80%) were inf ected 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 detec ted. Numbers of dead embryos recovered from experimentally infected, viremic SWR /J mice and from spontaneously endogenous MuLV-expressing AKR/J mice were s ignificantly higher, compared with numbers from nonviremic SWR/J control mi ce, and embryo lethality was significantly associated with prenatal proviru s expression. Postnatal inoculation of Akv induced lymphoblastic lymphomas in 15 of 24 (6 1%) SWR/J mice within mean +/- SD latency of 14 +/- 2.4 months. Only 3 of 3 9 (8%) control mice developed lymphomas (P < 0.005). Conclusion: Embryos in MuLV-viremic dams are readily infected, and inapprop riate prenatal expression of leukemogenic endogenous retroviruses may play a critical role in embryo lethality and decreased breeding performance in e cotropic provirus-positive mouse strains.