scholarly journals STUDIES ON HERPETIC INFECTION IN MICE

1943 ◽  
Vol 78 (4) ◽  
pp. 315-320 ◽  
Author(s):  
Howard B. Slavin ◽  
George Packer Berry
Keyword(s):  
Herpes Virus ◽  
Herpetic Infection ◽  
Olfactory Pathways ◽  
Suckling Mice ◽  
Herpès Virus ◽  
The Brain

Instilled intranasally into suckling mice, a mouse-passaged strain of herpes virus (HF) reaches the brain by both the trigeminal and olfactory pathways.

scholarly journals STUDIES ON HERPETIC INFECTION IN MICE

1943 ◽  
Vol 78 (4) ◽  
pp. 321-326 ◽  
Author(s):  
Howard B. Slavin ◽  
George Packer Berry
Keyword(s):  
Bone Marrow ◽  
Inclusion Bodies ◽  
Herpes Virus ◽  
Herpetic Infection ◽  
Suckling Mice ◽  
Direct Spread ◽  
The Central Nervous System ◽  
Herpès Virus ◽  
Renal Infection ◽  
Intranasal Instillation

Intranasal instillation of herpes virus in suckling mice results in specific lesions widely distributed in the viscera. The lungs are infected by aspiration of the virus. Virus disseminated by way of the blood establishes itself in endothelium in certain situations where parenchymal lesions result by direct spread from the vascular foci. Evidence of blood-borne infection was found frequently in the liver and spleen, less frequently in the suprarenals, and, in one instance, in the bone marrow. Renal infection appeared to be uriniferous. Lymph carriage of the virus also occurs, and lymph nodes draining infected areas were often found to contain herpetic inclusion bodies. Herpes virus seems incapable of invading the central nervous system of suckling mice by the vascular route.

scholarly journals CONTRIBUTIONS TO THE PATHOLOGY OF EXPERIMENTAL VIRUS ENCEPHALITIS

1928 ◽  
Vol 47 (1) ◽  
pp. 9-22 ◽  
Author(s):  
Simon Flexner
Keyword(s):  
Herpes Virus ◽  
The Other ◽  
Degree Of Protection ◽  
Recurrent Herpes ◽  
Pathogenic Action ◽  
Complete Failure ◽  
The Subject ◽  
Herpès Virus ◽  
The One ◽  
The Brain

In this paper, three strains of the herpes virus have been dealt with. The H.F. II strain was obtained from the subject H.F. 4 years after the H.F. I strain was secured. H.F. is a victim of recurrent herpes. If the subject is also a chronic carrier of the herpes virus, then it is not one, but two or more strains which are persistently carried. The H.F. II strain is of mitigated pathogenic action for the rabbit, as compared with the H.F. I strain; it is to be classed as dermatotropic rather than neurotropic. And yet, in the subject there was no indication that the attack of herpes provoked was different from the other attacks associated with the H.F. I virus. The other two herpes strains derive their interest from the fact that they came also from persons who suffer from repeated attacks of labial herpes. One strain proved highly neurotropic, resembling in this respect the H.F. I strain; the other was hardly neurotropic at all, but was none the less definitely dermatotropic. It may be possible at a later date to secure other samples of virus from these individuals for comparison. The dermatotropic F. strain penetrates to the central nervous system far more readily and certainly from the skin than from corneal surfaces. The recovered inoculated rabbits showed only relative protection to reinoculation of the herpes virus. A notable difference appeared in the degree of protection acquired, on the one hand by the cornea and on the other by the brain. While the one was partial, the other was complete. The complete resistance of the brain was shown (a) by the complete failure of the intracerebral inoculation, and (b) by the absence of circling movements following corneal inoculation.

scholarly journals CONTRIBUTIONS TO THE PATHOLOGY OF EXPERIMENTAL VIRUS ENCEPHALITIS

1925 ◽  
Vol 41 (2) ◽  
pp. 215-231 ◽  
Author(s):  
Simon Flexner ◽  
Harold L. Amoss
Keyword(s):  
Cerebrospinal Fluid ◽  
Herpes Virus ◽  
Virus Disease ◽  
Brain Structures ◽  
Epidemic Encephalitis ◽  
Virus Encephalitis ◽  
Human Pathology ◽  
B Virus ◽  
Herpès Virus ◽  
The Brain

In this paper is given an account of an inoculable virus disease produced in the rabbit with cerebrospinal fluid taken from a case of vascular and neural syphilis. The study which yielded the results presented was undertaken in the course of an investigation into the etiology of epidemic or lethargic encephalitis. Twenty-seven samples of cerebrospinal fluid, derived from cases of epidemic encephalitis, were tested by us upon rabbits without positive result. The one successful instance in which an inoculable disease was produced arose from the injection of one of three specimens of the cerebrospinal fluid taken from the case of syphilis. Following this success, two subsequent injections of the fluid, taken from the same patient, were made unsuccessfully. Although certain American and European investigators have reported securing a virus from the cerebrospinal fluid of cases of epidemic encephalitis, we have consistently failed in our endeavors to confirm their results. However, we believe that the finding of the J. B. virus may serve to clarify the obscurity and confusion now enveloping the so called virus of encephalitis. It had previously been shown that no biological differences could be detected between the herpes and the encephalitis strains of virus. The former, as is well known, is readily secured by inoculating rabbits with the contents of herpes vesicles, while the latter has, at best, been obtained with great difficulty. The J. B. virus agrees biologically with the herpes and encephalitis strains of virus. It is our opinion that the J. B. virus is merely a herpes virus which has gained access to the cerebrospinal fluid and, at the time of inoculation of the rabbits, was present in a concentration sufficing to induce virus encephalitis. The fact, if fact it is proved to be, that the herpes virus may find its way into the cerebrospinal fluid opens to question all the supposed instances of successful implantation of a virus of epidemic encephalitis upon the rabbit. It is indeed highly probable that, in so far as such a virus has been found at all in the cerebrospinal fluid, it also is a specimen of the herpes virus. Our studies lead us to suppose that at best it is an infrequent event for the herpes virus to occur in demonstrable form in the cerebrospinal fluid. Perhaps a more delicate means of detection than the rabbit inoculation would serve to reveal the presence oftener. It is known that strains of herpes virus of greater or less intensity of action for rabbits exist. It is, of course, possible that we discover, by present methods, only the highly active strains and those only when chancing to be present in a certain concentration. We inoculated 100 specimens of cerebrospinal fluid and obtained in a single instance the virus infection of the rabbit. In all respects the J. B. virus agrees in intensity of effect, in mode of attack upon the cornea, skin, and brain, and in immunization responses, with the true strains of herpes virus and the so called strains of encephalitis virus. If, as the above statements indicate, all the virus strains of the class considered are examples of the herpes virus, it follows that the etiology of epidemic encephalitis remains entirely unresolved. It is highly improbable that the ubiquitous herpes virus plays the kind of part in human pathology which it has been shown to play in experimental rabbit pathology. While the active strains of that virus possess a strong affinity for the brain structures of the rabbit, the virus has not in the past shown any selective affinity for the brain of man. To ascribe epidemic encephalitis in man to particular and peculiar varieties of the herpes virus is, with our present knowledge, unwarranted.20 The wide variations in histological lesions described in the brain of rabbits succumbing to herpes or virus encephalitis raise the question of the essential manner of action of the virus upon the brain tissues. Hitherto it has been the cellular infiltrative lesions which have been emphasized. We have, however, learned that very extensive infiltrations about blood vessels and in the brain substance may exist independently of even mild symptoms of disease.16 The question is propounded, therefore, whether the herpes virus does not attack nerve cells directly, affecting them quantitatively in such ways as at one time to produce stimulation and at another time paralysis. The manifold symptoms of virus encephalitis in the rabbit are open to this interpretation. In order, however, to base this notion on microscopical findings, a more subtle technique than hitherto widely employed is required. A histological restudy of the subject is being made with this view in mind. The name virus encephalitis is proposed for the experimental disease produced in rabbits by the inoculation of the herpes and allied viruses.

scholarly journals THE RELATION OF STREPTOCOCCI TO HERPES VIRUS ENCEPHALITIS

1928 ◽  
Vol 48 (2) ◽  
pp. 199-205 ◽  
Author(s):  
Peter K. Olitsky ◽  
Perrin H. Long
Keyword(s):  
Herpes Virus ◽  
Ground Substance ◽  
Intracerebral Injection ◽  
Ground Meat ◽  
Destructive Effect ◽  
Virus Encephalitis ◽  
Symptom Complex ◽  
Herpès Virus ◽  
Favorable Conditions ◽  
The Brain

Cultures of microorganisms similar to those described by Evans have been obtained in media inoculated with suspensions of herpes virus-infected brains prepared by grinding. But they have also been isolated from saline suspensions of uninoculated meat particles ground in a sterile mortar, and from dextrose broth treated in the same way. It is believed that these organisms are contaminants introduced during the process of grinding. Since they enter the material in no great number, one may suppose them to be suppressed by animals inoculated with the ground substance. In artificial media, on the other hand, they find favorable conditions for multiplication. In our experience, no growth of microorganisms is obtained in routine cultures of virus-infected brains, when fragments, instead of ground material, are used—a fact which may be taken to support the explanation just given. The tests of the part played by streptococci in experimental virus encephalitis failed to disclose that the microorganisms have any etiological relationship to the affection. The intracerebral injection of rabbits with the cultures procured in the course of the experiments produces a purulent type of meningoencephalitis which does not resemble virus encephalitis either in its symptom-complex or in its pathology. The same type of meningitis follows the injection of streptococci derived from ground meat particles, from "ground" broth, from normal brains, and those infected with herpes virus. Some rabbits manifested resistance to the streptococci, whereas all that have been inoculated intracerebrally with the three strains of herpes virus used in this study have proved susceptible thereto. Certain of the rabbits just mentioned which had proved resistant to streptococci inoculated into the brain or cornea were injected with herpes virus and reacted typically. Comparative tests have revealed that the streptococci are more sensitive to the destructive effect of 50 per cent glycerol than is herpes virus. From all this, it can be concluded that streptococci are not the visible form of herpes virus, nor do they produce in rabbits effects like those induced in the brain and cornea by the herpes virus.

scholarly journals CONTRIBUTIONS TO THE PATHOLOGY OF EXPERIMENTAL VIRUS ENCEPHALITIS

1928 ◽  
Vol 47 (1) ◽  
pp. 23-36 ◽  
Author(s):  
Simon Flexner
Keyword(s):  
Guinea Pig ◽  
Guinea Pigs ◽  
Herpes Virus ◽  
Epidemic Encephalitis ◽  
Virus Encephalitis ◽  
Active Virus ◽  
Brain Involvement ◽  
Herpès Virus ◽  
Experimental Virus ◽  
The Brain

The guinea pig is subject to cerebral and corneal inoculation of the herpes virus. The effects of the inoculations vary with the strength or degree of virulence of the virus. Weak strains of the virus are implanted on the cerebrum with difficulty and strong strains with ease. Weak strains are quickly suppressed by the brain and strong strains may be passed indefinitely from brain to brain of the guinea pig. Strains of intermediate potency can be passed for a limited number of times only. Weak strains induce keratoconjunctivitis without brain involvement, while strong strains invade the brain from the eye and produce fatal encephalitis. In the latter case, the brain contains active virus inoculable upon the cornea and into the brain of rabbits and guinea pigs. Strains of intermediate potency produce keratoconjunctivitis accompanied by mild symptoms of encephalitis, from which recovery results. The guinea pig serves even more definitely than the rabbit to distinguish grades of virus according to strength or virulence. There is no difference of kind but only of degree of response to inoculation of herpes virus in the rabbit and the guinea pig. The etiology of epidemic encephalitis has not, therefore, been brought appreciably nearer solution by experiments with herpes virus carried out in guinea pigs.

scholarly journals THE ACTION OF THE LEVADITI STRAIN OF HERPES VIRUS, AND OF VACCINE VIRUS IN THE GUINEA PIG

1928 ◽  
Vol 48 (3) ◽  
pp. 379-391 ◽  
Author(s):  
Peter K. Olitsky ◽  
Perrin H. Long
Keyword(s):  
Guinea Pig ◽  
Guinea Pigs ◽  
Herpes Virus ◽  
Vaccine Virus ◽  
Experimental Conditions ◽  
Two Samples ◽  
Vesicular Stomatitis ◽  
Cross Immunity ◽  
Herpès Virus ◽  
The Brain

A number of methods have been employed in attempts to induce encephalitis in guinea pigs with the Levaditi C strain of herpes virus. Some of these consisted of different modes of inoculation of the virus itself and others of different ways of combining it with vesicular stomatitis and neurovaccine viruses so as to obtain the concomitant effects of both. In still another test the Levaditi virus was combined with the neurovaccine in a manner calculated to bring about the maximum action of each at the same time. By all these methods, the Levaditi virus failed to evoke the characteristic encephalitis which this specimen is capable of inducing uniformly in rabbits. On the other hand, when the Levaditi herpes virus is inoculated into the brain of guinea pigs in conjunction with suitably timed corneal injections, it acquires active encephalitogenic properties. The results just noted suggest several considerations: 1. The possibility of increasing the virulence of a filtrable virus by animal passage in a special manner. It is not likely that the increase as observed was due to dosage, for after the virus acquired its encephalitogenic property for guinea pigs, the usual amounts of virus suspensions sufficed to induce, in a uniform way, typical encephalitis. 2. The opinion previously expressed by Flexner that the guinea pig serves merely to separate weak from strong strains of herpes virus is supported: for only according to the particular method described, could the encephalitogenic power of the Levaditi virus be developed and the weak be converted into a strong herpes strain. With the acquisition of this power, the Levaditi virus acted in precisely the same manner as strong herpes strains both in the guinea pig and the rabbit. Moreover, it was shown in guinea pigs that cross-immunity occurs between weak and strong strains. 3. The two samples of neurovaccine virus employed were incapable of inducing encephalitis in guinea pigs after intracutaneous, intratesticular, corneal, or intracerebral inoculation, although they were actively encephalitogenic in rabbits. In spite of the fact that the vaccine virus and herpes virus are different, as shown by the histopathology and absence of cross-immunity, they behave in the same way when injected into the brain of the guinea pig. The failure of the concomitant action of both viruses to induce encephalitis in the guinea pig suggests that the association of two viruses, under the experimental conditions outlined, is incapable of inducing encephalitis, if either, by itself, is non-encephalitogenic. 4. The serum from normal guinea pigs may neutralize a weak (Levaditi C) but not a strong (H.F.) strain of herpes virus; but the neutralizing action of the serum on Levaditi C virus is not uniform. 5. The Levaditi strain of virus can increase in quantity in the brain of the guinea pig to a degree which permits detection and yet fails to evoke any distinctive clinical picture or definite histopathological changes. 6. Repeated intraperitoneal injections of Levaditi virus in guinea pigs elicit no signs of infection, yet they induce a solid immunity to strong strains of herpes virus.

scholarly journals SYMPTOMATIC HERPES, A SEQUELA OF ARTIFICIALLY INDUCED FEVER

1940 ◽  
Vol 71 (2) ◽  
pp. 155-168 ◽  
Author(s):  
Stafford L. Warren ◽  
Charles M. Carpenter ◽  
Ruth A. Boak
Keyword(s):  
Inclusion Bodies ◽  
Herpes Virus ◽  
Ganglion Cells ◽  
Intranuclear Inclusion ◽  
Corneal Epithelial Cells ◽  
Corneal Epithelial ◽  
Acute Encephalitis ◽  
Fever Therapy ◽  
Herpès Virus ◽  
The Brain

1. Symptomatic herpes occurred in 190 (46.2 per cent) of 411 patients treated with fever induced by physical methods. 2. Herpes recurred in only 7, or 5.3 per cent, of 131 patients given subsequent fever treatments, suggesting that some immunity develops with the first attack. 3. An acute encephalitis-like syndrome of short duration and without sequelae developed in a group of patients with severe herpes following fever therapy. 4. A filter-passing virus, recovered from herpetic vesicles on patients treated with artificially induced fever, produced a fatal encephalitis in rabbits when inoculated intracerebrally and by corneal scarification. Intranuclear inclusion bodies were observed in corneal epithelial cells and in motor ganglion cells of the brain similar to those observed in rabbits injected with known strains of herpes virus. 5. Four strains of virus that had been recovered from herpetic vesicles appearing on patients subsequent to artificially induced fever were shown by cross-protection tests on rabbits to be immunologically related to the Frank strain of herpes virus.

scholarly journals STUDIES ON HERPETIC INFECTION IN MICE

1950 ◽  
Vol 91 (5) ◽  
pp. 527-537 ◽  
Author(s):  
Charles A. Evans ◽  
Howard B. Slavin ◽  
George Packer Berry
Keyword(s):  
Herpes Virus ◽  
Preliminary Treatment ◽  
Herpetic Infection ◽  
Adult Mice ◽  
High Virulence ◽  
Hind Foot ◽  
Herpès Virus ◽  
Foot Pad ◽  
Old Mice ◽  
Serial Brain

1. The severity of herpetic infection, of mice varied according to the site of inoculation, decreasing in the following order: cornea, skin of abdomen, pad of hind foot, tail. 2. The preliminary treatment of the foot pad or tail with methylcholanthrene increased the susceptibility to herpetic infection to a limited extent. 3. Two-week-old mice showed a much greater susceptibility to herpes virus inoculated on the tail or on the pad of the hind foot than did adult mice. 4. The HF strain of herpes virus, after more than 125 serial brain-to-brain passages in mice, possessed high virulence for cutaneous tissues of mice and showed no important differences in this respect from a recently isolated strain (Klee) of herpes virus.

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