Identification of trophoblastic giant cells as the initial principal target of early gestational murine enterovirus infection

Abstract

Theiler's murine encephalomyelitis virus (TMEV), a murine enterovirus, infects the majority of murine placentae and fetuses following inoculation in early gestation and infects most placentae but almost no fetuses in late gestation. The sequence of infection of TMEV following early gestation inoculation was studied. Mice were inoculated with TMEV on day 6 or 7 of pregnancy and sacrificed at intervals between 1 h and 4 days later. Culture of placenta-embryo units identified infection at 2, 3, and 4 days post-inoculation. In situ hybridization revealed TMEV RNA primarily in giant cells around the yolk cavity and in giant cells situated between the decidua and spongiotrophoblast layers of the placenta. Occasional decidual cells located near giant cells were also hybridization-positive. The giant cells were immunohistochemically identified as fetally derived trophoblast cells. Giant cells are the earliest predominant target of TMEV infection following early gestation inoculation and appear to be an integral part of the pathogenesis of gestational murine enterovirus infection.