The pregnant ferret as a model for studying the congenital effects of influenza virus infection in utero: infection of foetal tissues in organ culture and in vivo.

Organ cultures of ferret foetal tissues showed a similar pattern of susceptibility to influenza virus to that already observed for human foetal tissues (Rosztoczy et al., 1975); respiratory, alimentary and urogenital tissues supported the replication of influenza virus but nervous and lymphopoietic tissues (those which, in man, are associated with foetal or postnatal abnormalities) were insusceptible. In contrast to corresponding human tissues, ferret foetal placenta and amnion readily supported viral replication although both human and ferret umbilical cord were susceptible. In limited experiments, neither the membranes nor the susceptible foetal tissues became infected after intranasal inoculation of pregnant ferrets of various gestational ages. However, after intracardial inoculation of pregnant ferrets with high titre virus (ca 10(9) EBID50) virus was isolated from both foetal membranes and foetuses. The membranes became infected at early, middle and late gestation, but virus appeared to cross the placental barrier to infect foetal tissues only in late gestation. At this stage virus could be isolated not only from those foetal tissues (respiratory, alimentary and urogenital) susceptible in organ culture, but also in small amounts from tissues which were insusceptible in organ culture (heart, lymphopoietic and nervous tissue). Virus was also isolated from foetal membranes and foetuses of late gestation ferrets following intracardial inoculation with a one hundred-fold lower dose of virus which, unlike the higher dose, did not induce a maternal febrile response. The pregnant ferret appears to be a suitable model for investigating the effects on development of foetal infection with influenza virus but it may have disadvantages with regard to the nature and strength of the placental barrier.