Inclusion Bodies Alfred M

View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Digital Repository @ Iowa State University Volume 4 | Issue 1 Article 2 1941 Inclusion Bodies Alfred M. Lucas Iowa State College Follow this and additional works at: https://lib.dr.iastate.edu/iowastate_veterinarian Part of the Veterinary Infectious Diseases Commons, Veterinary Pathology and Pathobiology Commons, and the Zoology Commons Recommended Citation Lucas, Alfred M. (1941) "Inclusion Bodies," Iowa State University Veterinarian: Vol. 4 : Iss. 1 , Article 2. Available at: https://lib.dr.iastate.edu/iowastate_veterinarian/vol4/iss1/2 This Article is brought to you for free and open access by the Journals at Iowa State University Digital Repository. It has been accepted for inclusion in Iowa State University Veterinarian by an authorized editor of Iowa State University Digital Repository. For more information, please contact [email protected]. Inclusion Bodies How specific are inclusion bodies for the identification of virus diseases? Alfred M. Lucas, A. B., Ph. D.* N ORDER that we may both have in long to the pox group and a steady accu I mind the same thing during this paper mulation of facts for the past 35 years has it is probably well to set forth a brief now culminated in a reasonably satis description of inclusion bodies. In a broad factory understanding of the relationship biological sense the term applies to any of virus to inclusion body for this group formed mass of material, such as secretion of diseases. The development of this granules and plastids, but it is not in this sense that the pathologist uses the term; TABLE I for him it has come to mean those masses of material which are associated with virus Viruses Producing Inclusions In: diseases. Those in the cytosome, when Cytosome Only they are small, have practically no unique Vaccinia Sheep pox characteristics which will readily dis Fowl pox tinguish them from cytoplasmic accumula Molluscum contagiosum tions of non-virus origin but as they grow Infectious myxomatosis of rabbits Trachoma larger their size becomes a valuable cri Rabies terion. Those in the nucleus are more Louping ill easily identified in that they are usually Nucleus Only acidophilic and they usually seek a posi Varicella (chicken pox) Vesicular stomatitis tion in the center of the nucleus. There Infectious warts of dogs they lie free from the chromatin which Yellow fever Rift Valley fever migrates toward the nuclear margin. The Virus III of rabbits existence of an object which appears to Disease of parrots and parrakeets be an inclusion body is not proof of the Herpes simplex B-virus presence of a virus but merely an indica Pseudorabies tion that a virus should be considered if Borna's disease of horses no bacterial agent can be found. If all Poliomyelitis Fox encephditis virus diseases produced a similar type of Jaundice of silkworms inclusion body the problem would be sim Cytosome and Nucleus ple in that one could seek out that element Variola (small pox) common to all of them; but some are Alastrim (mild small pox) Submaxillary gland disease of guinea associated with inclusion bodies in the pigs cytosome, some in the nucleus, some in of ground moles both nucleus and cytosome and many pro Equine encephalomyelitis duce no inclusion bodies at all. Repre No Cell Inclusions St. Louis encephalitis sentative examples are given in Table 1. Mumps Most of the virus diseases which pro Rous sarcoma of fowls duce inclusion bodies in the cytosome be- Sac-brood disease of bees Many plant viruses "Department of Zoology, Iowa State College. Fall, 1941 11 knowledge will be reviewed briefly be reaction. It was this protecting substance cause it serves as a challenge to what we which made possible the separation of the should be able to do with the intranuclear inclusion from the cell by digestive en inclusions. Many years ago the elemen zymes and its absence in molluscum con tary bodies were discovered in smears and tagiosum (3) explains why the method it was suggested and later proved that would not work for this virus. It has these represented the actual virus agent. already been mentioned that corneal cells Their size was at the limit of microscopic add to the developing vaccinia inclusion visibility and filtration experiments have body a basophilic material (1) so that since showed that the poxes average interestingly enough we are led again to about 0.150 micron. When stained they the earliest interpretation of cytoplasmic are considerably larger than this. With inclusions expressed by Prowazek when the ultra-microscope objects as small as he named them Clamydozoa and explain 0.1 micron may be distinguished and ed that it was a cloaked organism-that the new electron microscope will probably the cell contributed a mantle over the make some of the smaller viruses visible. infective agent. Thus, for the pox group But to identify particles as small as these of viruses one can say that finding an within a cell and be convincing about it, inclusion body is comparable in diagnos is rather more difficult. Had the granules tic importance to finding the organism in remained uniformly dispersed in the cell anthrax or tuberculosis. they probably would not have been rec Not all cytoplasmic inclusions have re ognized. One of the early cytological stu vealed their secrets so well and the oppo dies (1) of vaccinia virus came to the site extreme is represented by the Negri conclusion that the basophilic inclusion bodies associated with rabies. The lyssa body was an aggregation of materials pro bodies and Negri bodies are sufficiently duced by the cell but that under the distinctive in their structural organiza stimulation of the virus abnormal amounts tion that they have been used satisfactorily were produced and these clumped togeth for diagnostic purposes but what they er. A contrary opinion (2) to this was are is still completely unknown as evi rendered for fowl pox when the cyto denced by the wealth of suggestions. Here plasmic inclusion bodies were separated are some: that the basophilic center is from the cell by digestive enzymes. The the organism and that the acidophilic inclusion bodies were washed repeatedly mantle is contributed by the cell; that the and then inoculated into the feather folli Nissl substance becomes modified into the cles of the fowl. One inclusion body Negri bodies; that the neurofibrils are would produce the disease. Efforts to converted into these bodies and finally handle the inclusion bodies of molluscum that they represent extruded nucleoli. contagiosum (3) in a similar manner were Their value for diagnostic purposes would not successful because the bodies fell probably be increased if one knew what apart into their separate elementary units. they are. Recently, by the growing of rabbit cornea Turning to the problem of the intranu in tissue culture (4), it has been possible clear inclusions we find that progress has to observe the multiplication of vaccinia been slow because the inclusions stain elementary bodies and their coalescence like oxychromatin which is a normal con into clumps within the cell. Consequently, stituent of the nucleus and because the there no longer is any doubt for this group idea that an organism would elect to re of viruses, at least, that the inclusion body side in the nucleus rather than in the is an aggregation of virus particles, but this cytosome has relatively little analagous is not the complete story; the cell contri data to support it. We do have the rickett butes something also. In fowl pox (5) it sias, however, as one good example of a was noted about 15 years ago that fats elab group of small organisms which are known orated in association with the Golgi ap to aggregate in the nucleus. Yet, in spite paratus moved toward the developing in of our limited knowledge on the subject, clusion body and gave to it a strong fat the idea developed that the presence of 12 The Veterinary Student an intranuclear inclusion was a fair indi of the published accounts are too sketchy cation that a virus was the etiological and very few photographs are sufficiently agent, even though the inclusion body in clear to show such small objects as part the nucleus may be merely a cell product. of a nucleus for the reader to form an Strong support for this idea came from independent opinion. Those papers, in the fact that none of the bacteria pro which the author has prepared drawings duced cellular reactions of this type and or even diagrams, are usually satisfactory. injections of various non-living substances Even examination of but one slide may usually failed to produce them. Then be misleading and it is often necessary to followed a period when many intranuclear make a fairly thorough study of the in inclusions were discovered apparently un clusion bodies with good optical equip associated with any virus disease. The ment to determine even the simple ques threatened agnosticism was circumvented tion of whether they are granular or amor when Cowdry proposed that intranuclear phous in type. inclusions be classified into two groups Of the two types, A has proven to be called type A and B (6). Type A included much more indicative of a virus than B those (a) which were granular and (b) (8) and the question always follows, "Are which produced a severe reaction in the the intranuclear inclusions aggregations cell leading to death. Type B were those of virus particles as they are in the poxes?" (a) which were amorphous irregular mas Attempts have been made to handle them ses or hyaline spheres and (b) which as Goodpasture did fowl pox but no suc produced only mild reactions in the cell.

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