CONTRIBUTIONS TO THE PATHOLOGY OF EXPERIMENTAL VIRUS ENCEPHALITIS
Authors: Flexner Simon , Amoss Harold L. 
Published: June 2004

In this paper we have sought to show that unequivocal strains of herpes virus exist in man, which, in the rabbit, exhibit a degree of encephalitogenic power not exceeded, and perhaps rarely equalled, by any strain of the so called encephalitis virus.
The fact that such highly encephalitogenic strains of the herpes virus exist in nature has, at the moment, theoretical and practical importance. Until recently, the view has been accepted by certain workers in the field that two biologically distinct viruses of this class occur—one inducing epidemic encephalitis and the other febrile herpes in man.
This view, is, indeed, being supplanted at the present time by the notion, advocated by Levaditi, Nicolau, and Poincloux, of a group of closely related virus organisms for which the name "herpetico-encephalitic" is proposed. Within this group they distinguish strains of virus displaying special affinities for the central nervous organs and others exhibiting equal affinities for skin and membrane (cornea) structures. The first mentioned strains are responsible, under suitable circumstances, for epidemics of encephalitis in man; the others give rise to ordinary attacks of febrile herpes.
The H. F. virus described in this paper does not conform to the classification indicated. While being a true febrile herpes strain, it possesses, nevertheless) a high degree of power to attack the central nervous system as well as marked capacity to implant itself on the skin and the cornea of the rabbit. Not only does virus encephalitis follow invariably upon the intracranial injection of the H. F. virus, but as regularly upon corneal, skin, nasal, blood, and testicular modes of inoculation. The symptoms of virus encephalitis thus provoked and the character of the brain lesions induced are precisely those, in all their detail and variety, including the presence of intracellular inclusion bodies, which have been described for the so called virus of encephalitis. Moreover, the H. F. virus is durably glycerol-resistant, is filterable through Berkefeld candles, and behaves immunologically as do the usual strains of herpes and of encephalitis virus.
On the basis of the experimental data presented, we conclude that any distinction made regarding, on the one hand, encephalitogenic power as a special property of a virus secured from cases of epidemic encephalitis, and, on the other hand, of ectotropic action as an equally special quality of a virus yielded by febrile herpes, is in its nature artificial and not in harmony with ascertained fact. What can, indeed, be distinguished are stronger and weaker strains of a virus) probably always herpetic in origin, as determined by the inoculation of rabbits. While a strong herpes virus is both dermatotropic and neurotropic, a weak virus tends, in its multiplication, to remain confined to the site of inoculation, to act chiefly on the tissues on which it is immediately implanted, and not to extend to distant parts. And this is equally true whether the strain of virus came originally from cases of epidemic encephalitis, or merely from cases of febrile herpes in man.
Hence direct comparison cannot be made between the stronger encephalitogenic and weaker non-encephalitogenic strains, according to any specific etiological property. The viruses we are discussing do, indeed, compose one group but it is the group of febrile herpes with which epidemic encephalitis is associated accidentally, if at all. It happens, indeed, that the Levaditi strain (souche) C and the Doerr Basel strain, both supposedly originating in cases of encephalitis in man, are less encephalitogenic for the rabbit than the true herpes strains, H. F. and Goodpasture M.