Congenital Rubella Infection of a Human Embryo

Abstract

MEDICLJOURNALwas not reliable enough for the diagnosis of sporadic cases of acute Sonne dysentery should be revised. Our confidence in the immunofluorescence technique described in this paper is such that it is our current practice to examine specimens from cases of acute diarrhoea immediately on arrival in the laboratory and to inform the doctor by telephone as soon as a positive result by fluorescence microscopy is obtained, emphasizing that such a report should be regarded as provisional and subject to confirmation by culture. With , 1964, 2, 166-167 The association between maternal infection with rubella (German measles) and the subsequent birth of a deformed child was first noted by Gregg (1941) and has been amply confirmed by later reports. Little progress could be made on studying the mechanism whereby these congenital defects were produced until satisfactory means were found for cultivating the virus in the laboratory (Weller and Neva, 1962;Parkman et al., 1962;McCarthy et al., 1963). During the spring and summer of 1962 a number of human embryos from pregnancies which were terminated after maternal exposure to rubella became available for study.Attempts were made to demonstrate the presence of virus in cultures prepared from this material. This paper describes the isolation of rubella virus from one of these embryos. Materials and MethodsEmbryo 13 was removed by hysterotomy performed 231 weeks after the last menstrual period on a mother who gave a history of an attack of rubella during the fifth week of pregnancy. Lung tissue was minced and trypsinized overnight at 4°C., and cultures were set up in Gey's solution containing lactalbumin hydrolysate and newborn calf serum (Porterfield, 1962). Subcultivation of cells was carried out, using essentially the method of Hayflick and Moorhead (1961). Cells homogenized in medium were frozen at -700 C. for later examination. ResultsHomogenates of third-passage-level human embryonic lung cells were used to infect cultures of rabbit-kidney cells of the strain GL RK13. These produced a cytopathic effect visible by direct and phase contrast microscopy, which was reproduced by the third to the fifth day in seven serial cultivations in rabbit cells. Control cultures subcultured at the same time remained negative.Neutralization tests were carried out, using serum from a rabbit immunized by five intravenous injections of GL RK13 grown rubella virus (strain "Judith ") which had been isolated in Liverpool. The seventh GL RK13 pass of HEL 13/3 virus was neutralized by this serum at a dilution of 1: 32, and a similar dose of "Judith" virus was neutralized by

Altered growth, differentiation, and responsiveness to epidermal growth factor of human embryonic mesenchymal cells of palate by persistent rubella virus infection.

“…Although there are several reports that describe establishment of diploid cells in RV carrier states, these cells were isolated from cogenitally infected human embryos and infants and showed comparably slow growth and limited life span (22)(23)(24)(25), and were therefore unsuitable for extensive study of the pathogenesis of the rubella syndrome. Since epidemiological and serovirological studies suggest that the congenital rubella syndrome is due to chronic or persistent infection ofhuman embryos with RV, establishment of a suitable RV-infected embryonic cell line of human origin with functional markers of differentiation and growth is essential to elucidate the precise mechanism of viral pathogenesis.…”

Studies of the Natural History and Prevention of Rubella

“…Table 12, -globulin had no significant effect on the incidence of rubella infection under the conditions of this prospective study. Moreover, as shown in Table 10, -globulin failed to prevent viremia, although it appeared to decrease the 34 (92 %) control degree or duration of viremia. During the course of these studies, a total of 37 children in the control groups and 33 children in the -globulin groups had comparable exposures to rubella.…”

Maternal rubella and its effect on the foetus.

“…Histological evidence was also obtained of inclusion bodies in foetal and decidual cells. Kay, Peppercorn, Porterfield, McCarthy, and Taylor-Robinson (1964) demonstrated virus in the lungs of a 23-weekold foetus removed by hysterotomy following maternal rubella at the 5th week. Heggie and Weir (1964) also noted the persistence of virus in foetal tissues.…”