Joel Warren

The relationships of the viruses of measles, canine distemper, and rinderpest.

Publisher Summary This chapter discusses the viruses of measles, distemper, rinderpest, and those other agents, such as the so-called “foamy” viruses that have in common a cytopathic effect in tissue culture consisting of syncytium formation and the production of intracytoplasmic and intranuclear inclusion bodies. It discusses the immunologic relationships of these viruses. It also attempts to illustrate graphically some of the known similarities and dissimilarities among members of the group. It has been shown that alterations in the virulence of these three viruses are easily accomplished by serial transfers in alien host systems. Further, the antibody patterns that follow from infection with attenuated strains may be both quantitatively and qualitatively different from those that are produced by natural infection. For this reason, virulent fresh strains may prove to be the ones of choice for future work on antigenic sharing within this group.

Passive Interferon Protection in Mouse Influenza.

Summary Interferon prepared from influenza virus infected eggs or mouse lungs when intranasally administered protected mice against a mouse-adapted Type B influenza challenge. To be effective, the interferons had to be given before virus, and treatments delayed 24 hours after virus exposure served only to aggravate the infection. The concentration of virus used in the challenge was critical. The effect was best observed when the dosage was approximately 10 LD50.

Adsorption of Myxoviruses on Magnetic Iron Oxides.

Summary Influenza virus will adsorb to powdered magnetic ferric oxide and can be eluted from the iron with appropriate concentrations of sodium phosphate or sodium carbonate. This reaction appears to be a physical adsorption and provides a simple method for concentration and partial purification of viruses.

The syncytial viruses.

August Compte has said, “Each of us is aware, if he looks back upon his own history, that he was a theologian in his childhood, a metaphysician in his youth, and a natural philosopher in his manhood.” Not only is this particular speaker well into his more reflective, and certainly less effective, years, but my assigned subject is one which invites a certain amount of philosophizing. What we euphemistically call the “Syncytial Virus Group” comprises some of the larger myxoviruses, as mumps and Newcastle disease virus (NDV), but it also includes measles, canine distemper, rinderpest, the parainfluenzas, and respiratory syncytial virus. As Plowright’ has pointed out, it does not customarily include agents of the herpes group which can also induce a syncytium in the sense that we are employing it, namely, “a multinucleate mass of protoplasm produced by the merging of cells.” Thus it seems appropriate to open this session by illustrating the typical cytopathic changes produced by these viruses in monolayers of simian and serial human cell lines and also to point out certain features that may eventually provide important differential characteristics within this heterogeneous family. In order to facilitate the digestion of this rather complicated situation, I have summarized certain of the differential growth features in TABLE 1. I t will be noted that canine distemper virus (CDV) and rinderpest are not included and this is because our personal experience with these agents in tissue culture has been restricted to the library. All of these viruses cause inultinucleated “giant cells” when grown in a human serial amnion cell, although the parainfluenza 1 strains did not induce this in monkey kidney tissue cells (MKTC) but rather a rapid type of diffuse degeneration with the appearance of swollen, stellate dendritiform cells. NDV also caused no cytopathogenic effects (CPE) in MKTC, confirming an earlier finding by Brandt.2 Only two viruses produced intranuclear inclusions, namely, measles and less frequently the shipping fever strain of parainfluenza 3 . Cytoplasmic inclusions were produced by four agents; measles, respiratory syncytial, CA strain of parainfluenza 2 and SF strain of parainfluenza 3. I t is interesting that the closely related HA-1 strain of parainfluenza 3 failed to induce inclusion bodies. Mumps and NDV were differentiated by the distribution of inclusions in single or fused cells although this may be a variable and chance observation. It would undoubtedly be profitable to investigate more deeply and with histochemical techniques the mode of formation of virus-induced syncytia. There is considerable reason to believe that much of this change is due to surface phenomena associated with particle attachment alone. In the case of measles, Toyoshima, Hata, and hLiki,3 and SchluederbergP have demonstrated that a noninfectious, hemolytic component of much smaller size than intact virus, can rapidly cause the formation of “giant” cells in primate cell monolayers without formation of complete virus. There is also suggestive

Immunization of monkeys with an inactivated measles antigen and their response to a subsequent measles infection.

Monkeys vaccinated with killed concentrated measles antigen uniformly develop neutralizing and complement-fixing antibodies. When vaccinated and control animals were exposed to live measles virus, the antigenically sensitized monkeys developed antibody faster and to a higher titer than normal animals. Viremia occurred in the presence of circulating antibody and it is suggested that leucocytes may serve to protect circulating virus.

Increased Susceptibility to Murine Hepatitis Virus Infection by Treatment with Iron Salts

Summary The administration of ferric ammonium citrate to newborn mice enhanced their susceptibility to MHV. Intraperitoneal inoculation of a chelating agent, EDTA, protected a significant proportion of newborn animals against MHV but only when administered shortly after birth.

VIRUSES OF THE ENCEPHALOMYOCARDITIS GROUP

The viruses commonly designated as Columbia-SK, MM, encephalomyocarditis, and Mengo encephalomyelitis (which I shall call the “EMC Group”) comprise a family of strains, the confused history of which affords an example of the needs for rigid and uniformly acceptable standards of identification and criteria of individuality. They also provide a group readily amenable to systematization. In fact, there are no specific characteristics within this generic group, and the designation of these viruses as separate strains rests, in the h a 1 analysis, on diversity of origin only. The worker given four unlabeled containers of each of these viruses would be unable to differentiate and tag them, using any of the techniques now a t our disposal. On the other hand, he would have little difficulty distinguishing the family from all other known genera of filtrable agents by the criteria of tissue tropism and serological character. Therefore, I do not propose to elaborate on the details of the various strains but, rather, to define the general properties of the group, and try to assess the differential value of their characteristics. The first of these agents to be isolated was recovered from wild cotton rats, which were being used for the passage of the Yale-SK strain of poliomyelitis virus. The new agent differed antigenically and in its pathogenicity from the Yale-SK, and was designated as the “ Columbia-SK virus.” A similar strain, “ MM,” was isolated shortly thereafter from hamster brain originally inoculated with human spinal cord and medulla from a fatal case of an undiagnosed paralytic disease. Because both strains were originally discovered under circumstances where either known or suspect poliomyelitis-infected material was being passaged through rodents, considerable confusion surrounded the relationship of those strains to poliomyelitis virus, and it was thought that they represented murine variants of the latter. Subsequent study has failed to provide evidence of any common antigen between the agents of the encephalomyocarditis group and poliomyelitis and, although similar in most physical properties, they appear to be unrelated viruses. The encephalomyocarditis (EMC) and Mengo encephalomyelitis viruses were both originally isolated from captive monkeys; the former in Florida, and the Mengo virus in Uganda. Subsequently, a strain of Mengo virus was obtained from mosquitoes and a wild mongoose caught in the vicinity of the monkey compound at Entebbe, Uganda. This wide geographic distribution would implicate a common generic host, and the pathogenesis of EMC viruses in the rat would suggest certain rodents as the natural reservoir. The occurrence of protective antibodies in wild rats of certain geographic areas and not in others lends considerable support to this theory. In the case of one strain, Mengo, arthropod carriage has been repeatedly demonstrated, and these may well serve as vectors in certain regions.

Reduction of tetrazolium salts by malarial parasites.

Abstract Free and intraerythrocytic forms of Plasmodium berghei and P. knowlesi reduced tetrazolium salts to their colored formazans when these cells were incubated with TZ under anaerobic conditions. Mepacrine hydrochloride incubated with P. berghei in vitro inhibited tetrazolium reduction. Plasmodia from mepacrine-treated hamsters had an impaired capacity to reduce TZ salts.

Antibody Response to Influenza Vaccines combined with Hexadecylamine.

Summary Hexadecylamine in levels up to .5 mg/ml is well tolerated by man and animals. A single injection into guinea pigs of influenza vaccines containing this material results in rapid production of antibody levels which exceed those elicited by control vaccines. Preliminary results in man suggest that adjuvants of this nature may be most efficacious in a population receiving primary influenza experience.