David Bodian

Portals of Entry of Poliomyelitis Virus in the Chimpanzee.

Summary Typical poliomyelitis has been produced in 4 chimpanzees by the intranasal, intragastric, and oral inoculation of untreated human stools. In 2 instances the olfactory portal was ruled out by section of both olfactory tracts.

Phosphatase Activity in Chromatolytic Nerve Cells.

Summary Markedly increased acid phosphatase activity has been found in regions of the cytoplasm of nerve cells in which chromatolysis has been produced by axon section. This increased activity is proportional to the degree of chromatolysis, and is thus probably associated with increased nucleoprotein synthesis or degradation.

Viremia, invasiveness, and the influence of injections.

In dealing with a phenomenon that represents a special case of the pathogenesis of poliomyelitis, it is important to emphasize that our knowledge of the fundamental processes is as yet incomplete and that, in preparing to develop the factors that underlie the ‘Lprovoking” effect of injections, we must distinguish sharply between established fact and hypothesis. Nevertheless, it is impossible to design satisfactory experiments dealing with the “provoking” phenomenon without making certain assumptions concerning the nature of the unmodified infection. In thinking about one of the capital problems of the pathogenesis of poliomyelitis, namely, the method by which virus penetrates into the central nervous system, we are confronted with the following wellestablished facts. First, in the presymptomatic period of human poliomyelitis infections and of infections in chimpanzees inoculated with invasive strains by virus feeding, virus can be readily isolated from the blood serum.’’ 2 , At this time, virus can also be isolated from the feces. The distribution of virus in human beings preceding this period of viremia is unknown and probably cannot be directly established. However, in chimpanzees sacrificed before any demonstrable virus can be isolated from the blood, virus can be shown to exist in high titer in the feces, in tonsillo-pharyngeal secretions, and in a few lymphatic structures closely associated with the alimentary tract, namely, the tonsils, deep cervical lymph nodes, Peyer’s patches, and mesenteric lymph nodes, but in no other viscera that we have examined in three carefully studied animals. Among the tissues that have failed to yield virus are portions of the intestinal walls, the trigeminal ganglia, and samples of practically every internal organ (TABLE 1). In other words, the distribution of virus in the previremia period suggests primary viral invasion and multiplication in the tonsils and in Peyer’s patches of the ileum, with lymphatic spread to local lymph nodes and subsequent spilling over into the blood serum. I t follows that the tonsils and Peyer’s patches may be not only the sources of virus in tonsillo-pharyngeal secretions and feces, but also the sources of a t least some of the virus that enters the blood stream. Evidence from chimpanzees and from human autopsy cases indicates that, subsequent to viremia, a number of “target” organs may be invaded secondarily by virus from the blood stream. These organs include the central nervous system and lymphatic tissues, and, confirming the work of Shwartzman and his colleagues described in this volume, the brown fat. Now we know that, in fatal human cases and in chimpanzees experiencing paralytic infection after virus feeding, respectively, it is not possible to recover virus consistently from peripheral nervous tissues that might be considered as leading from the alimentary tract to the central nervous system. This includes the coeliac ganglia, trigeminal ganglia, and olfactory bulbs. In both species,

Experimental Evidence on the Cerebral Origin of Muscle Spasticity in Acute Poliomyelitis.

Summary Evidence is presented which demonstrates that neither virus activity nor lesions in the spinal cord are necessary pathogenetic factors for the production of the spasticity of acute poliomyelitis. In 2 rhesus monkeys inoculated intracerebrally with poliomyelitis virus and killed in the preparalytic period when marked spasticity was present in the muscles of the legs, as well as elsewhere, no lesions were present in complete serial sections of the lumbosacral cord. In an additional similar case it was also found that no virus was present in the lumbosacral cord. In all cases severe lesions were already present in most of the brain centers usually involved, and neuronal destruction was especially severe in the midbrain tegmentum, reticular formation of the hindbrain, and in the vestibular nuclei. It is concluded that lesions in the brain alone can produce the spasticity of acute poliomyelitis. The pathological origin of this symptom is discussed, and evidence cited for the possible causative role of lesions in brain stem centers, especially the reticular formation.

Neutralization of three immunological types of poliomyelitis virus by human gamma globulin.

Summary A sample of gamma globulin, refined and concentrated about 23-fold from pooled adult human plasma, was tested for neutralizing antibodies against representatives of three distinct antigenic types of poliomyelitis virus, Brunhilde, Lansing, and Leon. The neutralizing potency was high against all three viruses. A dilution of the globulin solution of 1/100 neutralized 100 PD50 of virus in almost every instance. A dilution of 1/1000 failed to neutralize 100 PD50 of virus.

Poliomyelitis Virus in the Human Oro-pharynx.

Summary Throat swabs were taken from 14 cases of human poliomyelitis during the first week of the disease. Seven of these (50%) were found to contain active virus.

Neuronal Pathways as Determining Factors in Dissemination of Poliomyelitis in the Central Nervous System.

There has been hitherto no clear-cut evidence regarding the mode of progression of the virus of poliomyelitis from the portal of entry into and through the central nervous system (CNS) of man. In the experimental animal more information is available and there is now a general belief, supported by considerable evidence, that the principal rôle in the dissemination of the virus is played by neuronal pathways rather than by humoral ones, and that within the CNS there occurs a progression of the virus from the point of entry to certain susceptible regions, especially the motor centers in the hind-brain and spinal cord, where the most serious effects of the virus-host reaction become apparent. Little is known as yet concerning the determining factors in the transmission and localization of the virus throughout the CNS, although studies of some of the neuronal pathways involved have been made by Fairbrother and Hurst, 1 and by others. In this report, additional evidence bearing on these problems will be presented. The material examined up to the present time consists of some 50 brains of Rhesus monkeys in preparalytic and paralytic stages of poliomyelitis, induced by introduction of the MV virus intra-nasally, intracerebrally, intraocularly and intraneurally. In a few-cases the Wallingford strain (Trask and Paul 2 ), inoculated intracerebrally and by skin rub, was used. The brains were prepared under optimal conditions for histological study chiefly by the gallocyanin method of Einarson, 3 which satisfactorily demonstrates nerve cells, neuroglia, and inflammatory cells. In some cases various experimental procedures, such as section of the olfactory tracts, the corpus callosum, the bulbar pyramids, or the spinal cord, were carried out in order to modify if possible the mode of dissemination of the virus.

A note on the penetration of poliomyelitis virus from the gastrointestinal tract in the chimpanzee

Summary Evidence is presented that in the chimpanzee poliomyelitis virus may reach the central nervous system from the gut via the abdominal sympathetic nerves.

Wallingford Poliomyelitis Virus: Another Strain of the Lansing Type, Infective in Rodents.

Summary The Wallingford virus, isolated from the nervous system of a fatal poliomyelitis case in California in 1934, has been successfully passaged in cotton rats and in mice. Material from each of 2 paralysed cotton rats produced typical poliomyelitis in one rhesus monkey. The virus has been tested for immunological relationships by inoculation in monkeys vaccinated with, and shown to be immune to, the Lansing and the Brunhilde viruses, respectively. These two viruses are representatives of 2 distinct types of poliomyelitis virus. The Wallingford virus is indistinguishable from the Lansing virus by the vaccination-immunity test, and unrelated to the Brunhilde virus by the same test. A relationship between the property of rodent infectivity and the immunological specificity of the Lansing group of poliomyelitis viruses is suggested, in view of evidence for the existence of three distinct immunological groups of poliomyelitis viruses, only one of which has thus far been shown to be infective in rodents.

An Effective Method of Intraneural Inoculation of Poliomyelitis Virus.

The uncertainty of results obtained by most investigators with intraneural injections of poliomyelitis virus has limited the use of this method of inoculation for inducing experimental poliomyelitis. Neveretheless, if the virus of poliomyelitis is truly neurotropic, one would expect that intraneural inoculation would be as effective as intracerebral inoculation, and simpler, if the virus could actually be made to come into contact with numerous nerve fibers, rather than being forced along and between connective tissue sheaths within the peripheral nerve. This of course is strongly suggested by the work of Fairbrother and Hurst, 1 who showed that trauma during intraneural injection facilitates “takes” by this method of inoculation. Going one step farther, and with the knowledge that during the first few days after nerve section the nerve cells with axons cut are more susceptible to the virus than normal cells, 2 it was decided to determine whether simple section of a peripheral nerve and immersion of the central stump in virus suspension for a few minutes was sufficient to produce poliomyelitis. This method, which involves no mechanical injection pressure, and which places the virus in contact with the protoplasm of every axon in the nerve, was found to be highly successful in producing poliomyelitis. When a large nerve, such as the sciatic nerve, was used, this method of inoculation was invariably successful with two strains of known potency, the MV and Wfd 3 strains. In 9 Rhesus monkeys the sciatic nerve was sectioned with sharp scissors peripheral to the sciatic notch or at the mid-thigh level, and the central cut end then soaked in as little as 0.1 cc of 20% virus suspension for several minutes. Poliomyelitis resulted after an incubation period of 4-6 days.