The early appearance and subsequent distribution of murine leukaemia virus in NZB embryos

Abstract

AbstractInformation concerning both spontaneous autoimmune haemolytic disease and a uniquely high expression of solely xenotropic murine leukaemia virus (MuLV) is transmitted genetically in New Zealand Black (NZB) mice. The actual production, location, and dissemination of MuLV has now been monitored in NZB embryos by electronmicroscopy, which is the most suitable method for detecting such virus very early in prenatal life i.e. in eggs before they become implanted approximately 4 1/2 days after mating. A systematic search was made for intracisternal type‐A and type‐C virus particles in NZB embryos from the one‐cell stage to the 14th day of gestation. AKR, Balb/c, and F1 (BALB/cx NZB) eggs were included for comparison of preimplantation phases, and five combinations of blastocysts fused in vitro as 6‐ to 8‐celI eggs were also examined. Four variants of type‐A particles were distinguished, characteristically associated with the cisternae of the endoplasmic reticulum. All replicated at some stage of preimplantation development in NZB and AKR eggs, as well as in fused AKRAKR and BALB/c↔BALB/c blastocysts, and three of them were still to be found in 8‐ or 14‐day NZB embryos. Moreover, the smallest type‐A variant also appeared in one‐cell unfertilized NZB eggs, indicating that its production did not depend on the stimulus of fertilization. No type‐A virus was identified in normal BALB/c and F1 (BALB/cx NZB) blastocysts, or in NZBB́LB c, CBA/H‐T6CBA/H‐T6, and AKRCBA/H‐T6 combinants. By comparison, immature type‐C virus was first seen in 5‐day NZB implants. But it was not possible to decide whether implantation or a particular stage of differentiation determined its emergence, or whether it had only then reached detectable levels. Thereafter, immature C and type‐A particles coexisted and replicated until at least the 14th day of gestation, but mature C virus was not evident at this age. Both ecotropic and xenotropic MuLV can be represented morphologically as type‐C particles. The known lack of infectivity of the type‐A particles, coupled with our evidence of their genetic transmission and of their ubiquity in NZB embryos which do not harbour ecotropic Mulv, could indicate that they, too, are xenotropic. Coincidentally, huge numbers of immature and mature type‐C MuLV were found distending the uterine glands of pregnant NZB females carrying 5‐ or 7‐day implants. But a similarly extravagant picture was seen in agematched NZB virgins. These findings are to be investigated further.