Distemper Virus Research Articles

Immunological study of the agent responsible for subacute sclerosing panencephalitis and biochemical characterization of measles antibody in subacute scelerosing panencephalitis.

Antibody of restricted heterogeneity produced in high titers in response to a given antigen is commonly observed in patients affected with subacute sclerosing panencephalitis and is comparable to what is observed in rabbits hyperimmunized with bacterial vaccines. Subacute sclerosing panencephalitis immunoglobulins were isolated and partially sequenced. Their immunological activity was measured with measles virus, subacute sclerosing panencephalitis virus (LEC strain) and distemper virus.

Subacute sclerosing panencephalitis. Transmission of the virus to calves and lambs.

Ten calves and 15 lambs were intracerebrally inoculated with cell-free and cell-associated SSPE virus, measles virus, and distemper virus. Only animals inoculated with SSPE cell-associated virus showed neurological symptoms of myoclonic jerks, ataxia, decreased irritability, and blindness of the eyes. SSPE virus antigen could be located in the brains of two calves, and infectious SSPE virus was isolated from one calf after fusion of its brain cells maintained in tissue culture with indicator cells. None of the animals that received SSPE virus developed homologous antibodies. In contrast, animals inoculated with measles and distemper viruses, but who had no clinical symptoms, developed antibodies against the homologous virus. The occurrence of sporadic bovine meningoencephalomyelitis, histologically similar to experimental SSPE disease in cattle, is discussed as a possible link in nature in the causes of human SSPE.

Isoprinosine: lack of antiviral activity in experimental model infections.

This report is a condensation of data from a collaborative study proposed and sponsored by the Antiviral Substances Program of NIAID. The individual reports were prepared by the following persons: S. Baron and M. Worthington, NIAID, NIH; A. Friedman-Kien, New York University College of Medicine; J. C. Duenwald, Washington State University, L. A. Glasgow, M. Harmon, B. Janis, E. Kern, J. C. Overall, Jr., C. B. Smith, D. A. Stringfellow, and S. Westerberg, University of Utah College of Medicine; B. C. Easterday and E. H. Weinberg, University of Wisconsin.*Recently there has been much interest in isoprinosine as a broad-spectrum antiviral compound. The activity of this substance was evaluated in a coordinated study at five institutions. Experimental models in five species of animals were established using 11 viruses. Criteria for selection were: (l) representation of most major groups of viruses, (2) reproduction of natural routes of infection, and (3) simulation of potentially treatable viral infections of man. No therapeutic effect could be demonstrated in infections with encephalomyocarditis virus, type 2 Herpesvirus hominis, influenza, and rabies viruses in mice; vaccinia virus in rabbits; rhinotracheitis and panleukopenia viruses in cats; distemper virus in ferrets; and influenza and transmissible gastroenteritis viruses in swine. The only antiviral activity observed in this extensive series of experiments was suppression of fibroma virus lesions in rabbits given 600 mg/ kg per day of isoprinosine. Although antiviral activity is not precluded in other viral infections in animals or in man, these results clearly fail to substantiate the potential of isoprinosine as a potent, broad-spectrum antiviral substance.

Comparative immunofluorescent studies on measles, canine distemper, and rinderpest viruses. Immunofluorescence of measles, distemper, and rinderpest viruses.

The development of specific antigens of measles, canine distemper and rinderpest viruses in Vero cells was examined by fluorescent antibody (FA) techniques. Intracellular and extracellular virus antigens were demonstrated by FA staining of fixed cells and unfixed living cells, respectively. All the three viruses showed the same pattern of development of specific antigens in the same host cells. Both V and S antigens were considered to be synthesized exclusively in the cytoplasm.

The Development and Structure of Measles Virus

Measles virus and the closely related distemper and rinderpest viruses are members of the paramyxovirus group. A feature that distinguishes these viruses from other members of the group is the occurrence in infected cells of intranuclear inclusions. These are present in addition to the cytoplasmic inclusions which are a common feature of infection by all paramyxoviruses.In electron microscopic studies on thin sections of measles-infected primary monkey kidney cells and BSC-1 cells (a continuous line of monkey kidney cells) it was found that the intranuclear inclusions consisted of masses of tubular structures associated with a filamentous matrix. The tubules were 140 Å in diameter and had well-marked cross striations with a spacing of 50 Å. The latter were interpreted as rings of a helix forming the wall of the tubule. Aggregates of identical tubules and associated matrix material were observed in the cytoplasm of infected cells. In any one cell, tubules were usually present either in the nucleus or in the cytoplasm and there was no indication that tubules migrated from one site to another.

ジステンパーウイルス感染細胞の電子顕微鏡的観察

The pathomorphological changes of the dog kidney cells (MDCK cells) infected with distemper virus (Hokkaido strain) were examined in the electron microscope.In the inclusion bodies, randomly arrayed tubular filaments were recognized and the virus particles were not seen. Many of the infected cells which contained inclusion bodies developed a lot of spherical shaped virus particles on and the outside of the cell surfaces.The virus particles which negatively stained with PTA showed the nucleocapsids inside of them. The tubular filaments in the inclusion bodies were closely resemble the nucleocapsids of the virus particles in size and shape.

The effects of canine distemper virus on explant tissue cultures of canine cerebellum.

Canine cerebellar explant cultures were employed as a model for studying the effects of the virus associated with demyelinating canine distemper encephalomyelitis. Cultures which were inoculated after four to seven days of growth with distemper virus (Lederle strain) had beginning cytopathic effect (CPE) in the peripheral outgrowth on the eighth post-inoculation day. The cells predominantly affected were astroglia and mesenchymal cells. The cellular lesions consisted of inclusion body development (intracytoplasmic and intranuclear), syncytial giant cell formation, and production of a reticular pattern in the outgrowth. Astrocytes subsequently became affected in the inner outgrowth and explant. Cellular degeneration was common, but a high degree of apparent coexistence of virus (inclusion bodies) and cells was a characteristic feature.

麻疹およびジステンパーウイルス粒子の形態的比較観察

麻疹およびジステンパーウイルス粒子の形態的比較観察

麻疹並びにジステンパーウイルス感染細胞の細胞化学的研究

麻疹並びにジステンパーウイルス感染細胞の細胞化学的研究

Einschlusskörperchen bei Hunden mit Staupe-Enzephalitis und anderen Erkrankungen des Zentralnervensystems

A histologic study was made of the central nervous system of 108 dogs with neurological illness. One group comprised 71 cases of distemper encephalitis. The second group of 37 cases encompassed toxoplasma encephalitis (14), symmetrical cerebral necrosis (10), reticulosis (6), lymphocytic meningoencephalitis (3), leukoencephalitis (2) and canine viral hepatitis (2). Inclusion bodies can be found in all dogs with distemper encephalitis. In most cases this diagnosis is easy, even without the inclusion bodies. However, detection of inclusions becomes important in cases showing a form of distemper encephalitis atypical with respect to histologic type or localization. In one case each, focal symmetrical necroses and toxoplasmosis-induced lesions were observed in association with distemper infection of the CNS. The regularity with which inclusion bodies can be found in all cases of distemper encephalitis means that in their absence, lesions induced by the distemper virus can be excluded with considerable assurance. The dependence of the density of the inclusion bodies on the type of tissue changes, the histochemical and tinctorial features of the inclusion bodies, the occurrence of lesions in the cerebellar granule cells, and the formation of cell syncytia by glial cells with inclusion bodies are discussed with respect to their specificity for distemper viral infection of the CNS.

Toxoplasmosis in Distemper-Susceptible Carnivora

Toxoplasmosis is described in 18 carnivora of five different species: five dogs, four gray foxes, two raccoons, a skunk and six mink. In the raccoons and skunk the infection is reported for the first time, and in the mink for the first time in the United States. All the cases represented the acute disseminated form of toxoplasmosis, with focal necrosis of the lung, liver, and heart, and glial nodules of the central nervous system. A simultaneous distemper infection was present in three of the five dogs, in all four gray foxes, in both raccoons, and the skunk. It is believed that the distemper virus may provide the most important triggering mechanism necessary to initiate an acute toxoplasma infection or cause a flare-up of latent toxoplasmosis. In a 3-week-old puppy, and in the mink the toxoplasma infection was not associated with canine distemper.

REVISÃO DE DADOS DA EPIDEMIOLOGIA E ETIOLOGIA DO SARAMPO E SUBSíDIOS PARA A VACINAÇÃO CONTRA A DOENÇA

Measles mortality rates are alanning in Brazil. The disease occupies in different counties, from second to fourth place as cause of death among infectious and parasitic diseases. Measles kills in Brazil more than Diphteria, Poliomyelitis, Tetanus, Pertussis and Small:pox. The majority of deaths occur at the age of 0-2 years. It was reminded the natural story of measles prevention up to the vaccines they tried. Relations between measles and distemper viruses were commented, including the results of the prior experiences of one of the authors of the work. Comparison between neutralisation and hemagglutination-inhibition tests showed paralel results. Serological appraisal on measles live-virus vaccine and inactivated vaccine showed higher percentage of conversions with live-virus vaccine. On the other side no untoward effects could be demonstrated with the inactivated vaccine; they emphasized the necessity of 3 dosis o f inactivated vaccines to get higher percentage of conversions. Despite fever and scanty rash1 children could play, without catarrhal fenomenons or intensive malaise, when vaccinated with live-virus-vaccine. Electrocardiographic and X-ray studies did not show abnormalities among the live-virus vaccinees. The incidence rates of measles in the nursery dropped from 30 to 50 each year to zero during 1962, when vaccination was started. Only three cases of mild measles were observed in that nursery among the vaccinees during the first 5 months of 1963.

Influence of Amount of Test Virus on Quantitative in ovo Canine Distemper Virus Neutralization Test

SummaryIn experiments under precisely controlled conditions, an inverse linear slope 1 relationship between log canine distemper (CD) virus concentration and log CD neutralizing antibody titer was not demonstrated. The data indicate that a method of mathematical interpolation whereby serum titers are converted to “antibody units” will not be in accord with experimentally determined in ovo test results. Possible standard procedures that might make possible direct comparison of test results reported by different laboratories are discussed.

Subclinical infection of dogs by canine-adapted measles virus evidenced by their subsequent immunity to canine distemper virus.

Moura, Roberto A. (Chas. Pfizer and Company, Inc., Terre Haute, Ind.) and Joel Warren. Subclinical infection of dogs by canine-adapted measles virus evidenced by their subsequent immunity to canine distemper virus. J. Bacteriol. 82:702-705. 1961.-Young dogs were inoculated with virulent measles virus which had been adapted to canine kidney or human amnion cell culture. None of the animals showed any clinical symptoms nor could virus be isolated from the blood, although measles-neutralizing and complement-fixing antibodies developed during convalescence. All dogs failed to develop antibody to canine distemper. However, when these and normal control animals were subsequently inoculated intracerebrally with virulent distemper virus, each of the controls succumbed to typical symptoms, whereas all of the measles-immune dogs survived. These results suggest that the cross-protection conferred by measles against canine distemper virus infection involves factors other than humoral antibody. The immunity persists for a considerable length of time.

Prospects for measles immunization with reference to the relationship between distemper and measles viruses

The results of several cross-immunologic experiments in various animal species and in tissue culture failed to confirm the relationship between measles and distemper viruses that has been reported by others, dimming the hope that distemper virus might be used as an effective prophylactic against measles. In contrast, vaccination of children with attenuated measles virus promptly induced measles antibodies, even when the concentration of virus administered was only 6 TCD50. In most instances, vaccination evoked mild clinical symptoms similar to those in gamma globulin-modified measles, the most prominent of these being fever that ranged from 38° to 40° C. and lasted one or two days. Rash also was recorded in a number of children, but Koplik spots and catarrhal signs were unusual. Affected children did not appear to be toxic or acutely ill; this was the case even in those who had significantly elevated temperatures. No virus was recovered, either from nasopharyngeal swabs taken on the seventh, ninth, and eleventh days after vaccination or from third-day blood samples, and no cases of secondary measles occurred in either institutionalized children or those living with their families. Questions about the vaccine still to be answered concern the duration of the immunity provided, the possibility of postvaccination encephalitis, and the ability of vaccinees to transmit the infection. Answers depend on the gradual and careful extension of trials in susceptible children. The results of several cross-immunologic experiments in various animal species and in tissue culture failed to confirm the relationship between measles and distemper viruses that has been reported by others, dimming the hope that distemper virus might be used as an effective prophylactic against measles. In contrast, vaccination of children with attenuated measles virus promptly induced measles antibodies, even when the concentration of virus administered was only 6 TCD50. In most instances, vaccination evoked mild clinical symptoms similar to those in gamma globulin-modified measles, the most prominent of these being fever that ranged from 38° to 40° C. and lasted one or two days. Rash also was recorded in a number of children, but Koplik spots and catarrhal signs were unusual. Affected children did not appear to be toxic or acutely ill; this was the case even in those who had significantly elevated temperatures. No virus was recovered, either from nasopharyngeal swabs taken on the seventh, ninth, and eleventh days after vaccination or from third-day blood samples, and no cases of secondary measles occurred in either institutionalized children or those living with their families. Questions about the vaccine still to be answered concern the duration of the immunity provided, the possibility of postvaccination encephalitis, and the ability of vaccinees to transmit the infection. Answers depend on the gradual and careful extension of trials in susceptible children.

Newer Virus Diseases—Clinical Differentiation of Acute Respiratory Infections.

Dr. Adams' compact text admirably Summarizes recent advances in clinical virology for the practicing physician. Not only are the well-recognized viral respiratory infections reviewed, but the reader is reminded that viruses usually associated with syndromes primarily involving other organ systems on occasions may produce only respiratory symptoms. The text is particularly timely with its inclusion of the newly identified members of the myxovirus family, and it emphasizes the importance of these agents. The author's personal investigations considerably enrich the sections on sudden death in infants, giant-cell pneumonia, and infections with measles and distemper viruses. Although the central theme is a review of acute respiratory illnesses produced by viruses, bacteria, and fungi, the implications of the title cannot be completely fulfilled. The reader will be promptly impressed that although distinct clinical syndromes do exist, the accurate clinical differentiation of acute respiratory infections still requires laboratory confirmation. Some sections are covered only

The Life History of the Salmon-Poisoning Fluke, Nanophyetus salmincola (Chapin)

The life history of Nanophyetus (= Troglotrema) salmincola (Chapin) has been studied by several workers who were interested chiefly in a disease of canines transmitted by this trematode (Simms, Donham and Shaw, 1931; Cordy and Gorham, 1950; and Philip et al, 1954). The etiologic agent has been considered by various workers to be distemper virus (Suckley, 1855), a bacterium (Bonebrake, 1925), an ameba (Pernot, 1911), mechanical destruction (Hoeppli, 1926), a haemosporidian or rickettsia (Simms and Muth, 1933), a rickettsia (Cordy and Gorham, 1950), and Neorickettsia helmintheca, Philip, Hadlow and Hughes, 1953. The role of the fluke is still not clear, but its association with salmon-poisoning disease was established in 1925 by C. R. Donham (see Donham, 1928). Donham's fluke was named Nanophyes salmincola by E. A. Chapin (1926), who (1928) amended the generic name to Nanophyetus. This animal, along with Nanophyetus schikhobalowi Skrjabin and Podjapolskaja, 1931, from Siberian aborigines, was subsequently transferred to Troglotrema Odhner, 1914, by Witenberg (1932) who believed T. schikhobalowi to be conspecific with T. salmincola. Wallace (1933) considered Troglotrema for a related fluke, Sellacotyle mustelae Wallace, 1935, and retained the genus Nanophyetus for salmincola. The molluscan host was believed (Simms, Donham and Shaw, 1931) to be Oxytrema (= Goniobasis) silicula (Gould) as a result of work and unpublished drawings of Sinitsin (Wallace, 1935). There was confusion (Donham, 1928) as to which of several cercariae was that of N. salmincola. Sinitsin's (1930) descriptions of the larval forms are indeed confused. The important fish hosts were known to be species of Salvelinus, Salmo, and Onchorhynchus. Distomulum oregonensis, proposed for the metacercariae by Ward and Mueller (1926) who believed them to cause pop-eye disease of trout, was relegated to synonymy (Price, 1929). The purpose of this research was to complete the life history of Nanophyetus salmincola and to illustrate the various stages.

Comparative studies on measles and distemper viruses in suckling mice

Measles virus propagated in human embryonic kidney tissue has been adapted to suckling mice through serial intracerebral passages. The agent propagated in mouse brains has been identified as measles virus by serological tests. A reproducible mouse test for the measurement of measles virus neutralizing capacity has been elaborated.

Distemper and measles viruses. I. lack of immunogenic crossing in dogs and chickens.

SummaryPuppies, vaccinated against canine distemper (CD) or immunized and challenged with CDV, developed high levels of homologous antibodies but failed to develop CF or serum neutralizing antibodies for measles virus (MV). Similarly, chickens hyperimmunized with CD virus did not develop measles neutralizing antibodies, although CD antibodies in appreciable levels appeared in 6 of 6 birds. Hyperimmunization of another group of chickens with MV was followed by no neutralizing CD antibodies in any of 6, whereas 5 of 6 birds gave a substantial measles response.

Immunological relationship between measles and distemper viruses.

SummaryIn tissue culture studies, the Edmonston strain of measles virus was neutralized by distemper antiserum prepared in ferrets with the egg-adapted and mouse-adapted strains of distemper virus. All normal ferret sera failed to show any neutralization of measles virus. In animal studies, ferrets immunized with measles virus and subsequently challenged with virulent distemper virus showed some evidence of protection as revealed by prolonged incubation periods, modified illnesses and survivals. The mouse-adapted distemper virus was completely neutralized by measles antiserum prepared in ferrets, whereas, normal serum failed to show any neutralization. Mouse-adapted distemper virus was also neutralized by human measles convalescent sera. These results suggest that common antigenic components are shared by the viruses of measles and distemper.