A FILTERABLE VIRUS PRESENT IN THE SUBMAXILLARY GLANDS OF GUINEA PIGS
Authors: Cole Rufus , Kuttner Ann G. 
Published: June 2004

In the lesions of herpes simplex and similar conditions due to filterable viruses, cells are present which show characteristic alterations, particularly in the nucleus. The nucleus of these cells contains a mass which stains with acid dyes. Surrounding this mass is a clear space or halo, within which there are large granules staining with basic stains. These cells are little if at all enlarged.
In a few human cases, especially in infants, enlarged cells have been found which contain nuclei showing changes similar to those seen in the abnormal cells of herpes simplex.
In the ducts of the submaxillary glands of guinea pigs, Jackson observed structures which she considered to be protozoan parasites. Our own studies indicate, however, that these structures are greatly swollen epithelial cells with nuclei having the same characters as the nuclei of the atypical cells in the lesions of herpes simplex. These cells are usually surrounded by a mononuclear cellular reaction. They were found in 84 per cent of the full grown guinea pigs examined but they were present in only three of forty-three young guinea pigs less than 1 month old. The resemblance of these cells, except as regards size, to the atypical cells present in lesions due to filterable viruses suggested that they also may be the result of an infection with a similar agent. That they are usually not present in guinea pigs less than 1 month old indicates that natural infection usually occurs after this period.
Experiments were therefore undertaken to determine whether or not an infective agent is concerned in this condition and if so to learn something of its nature. When an emulsion of the submaxillary glands of full grown guinea pigs is injected into the brains of young guinea pigs the animals have fever and exhibit symptoms of cerebral irritation. They usually die in 5 to 7 days and in sections of the brain a diffuse subacute meningitis is found. In the exudate there are large numbers of cells having all the characteristics of the abnormal cells of herpes simplex. Similar cells are present in the lesions resulting from the injection of the same emulsion into the testicle, lung, tongue, and submaxillary glands of young guinea pigs. In none of these lesions, however, are the cells greatly enlarged as they are in the lesions in old guinea pigs.
These results support the view that the lesion in the submaxillary gland of old guinea pigs is due to an infective agent. Attempts were therefore made to transmit this agent through a series of young guinea pigs. When the injections were all made into the same organ all the experiments but one gave negative results, but when the site of injection was changed at each transfer it was possible in a number of instances to reproduce the lesions through two animals in series and in one experiment through three animals in series. By modifying the technique, efforts were made to transmit the infection indefinitely but these attempts were unsuccessful. No explanation can be offered for this failure.
Studies made to determine some of the properties of the infective agent have shown that it is destroyed by heating at 54° for 1 hour, and that it is not injured by preservation in 50 per cent glycerol for as long as 11 days. After the material had remained in 50 per cent glycerol for 28 days, however, it was found to be no longer infective. The infective agent was not held back by a Berkefeld N filter which was impermeable to bacteria. It seems probable therefore that the infective agent belongs in the group of filterable viruses, though further work will be necessary to learn more of its exact nature. These observations present additional evidence that the presence of cells with nuclear inclusions in any lesion indicates that the injury is probably due to an infective agent belonging in the group of filterable viruses.