Histologic Findings in Livers and Spleens of Guinea Pigs after Infection by the Marburg Virus

Abstract

In this paper we report on investigations with the Marburg Virus which were closed shortly before this symposium. Our results originate from 26 guinea pigs, which especially in the 1st, 3rd and 4th, partly also in the 5th, 6th as in the 9th passage were infected intraperitoneally, intravenously or intracerebrally and either died or were killed between the 2nd and 21st day of illness. Our interest was on the one hand to see how far the morphological changes in the livers and the spleens agree with the findings in human beings and on the other hand whether we could discover other peCUliarities. At first it could be seen-as already known-that connections exist between the kind of infection and the climax of the changes. So we found the most severe changes in the early sequence on the 7th and 8th day of illness, in the late passage already on the 5th day of illness. In the liver we found single-cell necroses which were disseminated and sC:lttered all over the lobules. We constantly demonstrated side by side different stages of the development of the necroses. The single cell necroses were marked by a homogeneous transformation, an increased eosionophilia of the cytoplasm and pyknotic nuclei. Later on they looked like the Councilman bodies. At a greater magnification it was seen that the liver cells showed circumscribed regressive changes of the cytoplasm in the form of condensations or clottings shortly before the total necrosis. Besides multiple single-cell necroses, group necroses developed. When they only covered a few liver cells, an activation of the Kupffer cells always appeared very early; when there was a larger area affected, it first came to a sudden decay of the necrotic liver cells. After this a considerable proliferation of the Kupffer cells filled the raised defects. Inflammatory cell collections could seldom be proved within the sphere or in the vicinity of the necroses. Here and there liver-cell mitoses existed in the vicinity of the necrotic areas. In all cases with liver necroses, a fatty degenera-tion of the liver cells was to be seen at the same time. The periportal tracts showed only a slight inflammatory reaction with monocytoid elements. Cholestasis could be seen in no case. In the livers of the animals killed on the 17th or on the 21st day of illness, the only sign of liver damage was a circumscribed proliferation of Kupffer cells. Therefore we conclude that these changes may be reversible. As the changes in the guinea pig livers were chiefly marked by disseminated single-cell and group necroses of liver cells with a conspicuously slight inflammatory reaction, an early proliferation of Kupffer cells and a more or less marked fatty degeneration, there is a remarkable correspondence with the findings in the human liver caused by this infection (BECHTELSHEIMER 1968, GEDIGK, BECHTELSHEIMER and KORB 1968, KORB, BECHTELSHEIMER and GEDIGK 1968). G. A. Martini et al. (eds.), Marburg Virus Disease © Springer-Verlag Berlin Heidelberg 1971 124 G. KORB and W. SLENCZKA Besides this, in five cases we could find small basophilic corpuscles-similar to the human material-partly in the periportal tracts, occasionally in the liver cells. Rarely small eosinophilic bodies surrounded by narrow uncoloured areas could be seen in hepatocytes. At present it is not possible to explain their importance. Other liver cells contained granular or irregular basophilic structures which showed positive PAS and v. Kossa reactions. Just the same structures were described by SIMPSON, ZLOTNIK and RUTTER (1968) and ZLOTNIK (1969). They consider that there are connections between the basophilic structures and accu-mulations of the infective agent. Finally, we found here and there so-called fibrinoid thrombi inside the sinus-oides and enlarged Kupffer cells which had phagocyted a hyaline fibrinoide material. Even in the spleen, the changes resembled the human material. Thus we could prove multiple partial follicular necroses; at the same time we found a slight but significant amount of cells in the red pulp on the 7th day of illnes. The red pulp contained a moderate eosinophilic, partly homogeneous, partly more granular material. In a further phase we found at first in circumscribed areas and later on diffuse multinuclear giant cells as well as reticular and monocytoid cells in the red pulp. Corresponding changes were found in one animal on the 17th day of illness and a beginning fibrosis of the pulp could be seen in another animal on the 21st day of illness. In 10 of the 26 guinea pigs we saw basophilic corpuscles in the spleens, chiefly between the 6th and the 9th day of illness-similar to those we described in the liver. They were partly diffusely scattered in the red pulp. Finally, we could identify cells which contained a hyaline fibroid material. Summary: it follows from our investigations that morphological changes in the liver and the spleen of guinea pigs caused by an infection of the Marburg Virus show a remarkable conformity with the findings in human beings. Further peculi-arities were discovered, but the explanation can only be found by new experiments and by the use of additional methods. References