Poliomyelitis Virus In Tissue Culture Research Articles

Growing Pathogens in Tissue Cultures: Fifty Years in Academic Tropical Medicine, Pediatrics, and Virology (review)

Reviewed by: Growing Pathogens in Tissue Cultures: Fifty Years in Academic Tropical Medicine, Pediatrics, and Virology Michael Bresalier Thomas H. Weller . Growing Pathogens in Tissue Cultures: Fifty Years in Academic Tropical Medicine, Pediatrics, and Virology. Edited by Anthony L. Komaroff, with Ellen Barlow. Canton, Mass.: Science History Publications/USA, for the Boston Medical Library, 2004. xi + 292 pp. Ill. $35.00 (0-88135-380-9). It was fifty years ago that Thomas Weller shared the Nobel Prize in Medicine and Physiology with John Enders and Fredrick Robbins for their discovery of a technique for growing poliomyelitis viruses in tissue culture. The technique facilitated the manufacture of the Salk and Sabin polio vaccines—yet, as Weller's autobiography shows, the impact of tissue culture on medical virus research extended well beyond these biomedical icons. Tissue-culture techniques played a key role in virology's formation as a discipline in the 1950s: they revolutionized virus assays and vaccine production; they helped put workable diagnostic tools for virus diseases in the hands of hospital and public health laboratories; they were vehicles for making virology relevant to medicine. Weller's autobiography is a testament of these developments. It also reminds us of the ways in which a discovery can shape and make a medical scientific career. Weller spent the better part of his working life at two Harvard institutions, the Research Division of Infectious Diseases at Children's Hospital and the prestigious Harvard School of Public Health, and the main parts of this book follow him through these institutions. He provides a window onto the social life there, albeit one framed by his personal and professional interactions. Following a brief introduction to his childhood and student days, Weller devotes part 2 to his development as a virus worker. The story concentrates on his life in the laboratory at Children's Hospital, where he stayed until 1954. He trained here under Enders in the late 1930s; after the war, Enders brought him to the Research Division in 1947. Working with Robbins, and guided by Enders, in 1949 Weller devised the team's revolutionary technique. Besides isolating poliomyelitis virus, he used variations of the technique to isolate varicella-zoster virus, rubella virus, and the cytomegaloviruses. Weller's discussion of his apprenticeship in virus research, the making of tissue cultures, and his important studies of virus diseases illuminates key aspects of mid-twentieth-century virus work. One of the strengths of part 2 is the insight it gives into the process, and the politics, of postwar medical virus research. Weller revisits the well-known controversy around the testing and production of Salk's vaccine. While he kept his views private at the time, he links the infamous Cutter incident to shortcomings in Salk's clinical trials and the rush to get the vaccine into wide use. Weller's early successes opened doors at Harvard, which saw him quickly move from being a laboratory researcher to an institute-builder, administrator, and key player in Harvard's School of Public Health. Part 3 describes this shift. In 1954, he became Strong Professor and Chairman of Tropical Public Health. The position gave him leverage to expand the department into the unrivaled center of American tropical medicine. Besides the institutional story, Weller describes the changing fortunes of tropical medicine and international health in the latter half of the twentieth [End Page 365] century. During the Cold War, tropical public health initiatives received considerable support from the U.S. government and private patrons—yet by the early 1980s, American tropical medicine had but a marginal place in medical curricula and governmental funding. Unfortunately, Weller offers few explanations for this decline. He does argue, however, that this shift in priorities has had implications for the capacity of the United States to respond to emerging infectious diseases. He ends on a cautionary note: he pleads for a return to the basic principles of tropical medicine that he sought to create at Harvard, which combine an approach to disease in ecological terms with programs aimed at Third World development. These are laudable goals. Autobiographies of eminent scientists tend to make for poor history. Weller's story is often anecdotal and episodic. Still, it represents a...

The Cultivation of the Poliomyelitis Viruses in Tissue Culture

Journal Article The Cultivation of the Poliomyelitis Viruses in Tissue Culture John F. Enders, John F. Enders Please address requests for reprints to Reviews of Infectious Diseases, Channing Laboratory, 180 Longwood Avenue, Boston, Massachusetts 02115. Search for other works by this author on: Oxford Academic PubMed Google Scholar Frederick C. Robbins, Frederick C. Robbins Search for other works by this author on: Oxford Academic PubMed Google Scholar Thomas H. Weller Thomas H. Weller Search for other works by this author on: Oxford Academic PubMed Google Scholar Reviews of Infectious Diseases, Volume 2, Issue 3, May 1980, Pages 493–504, https://doi.org/10.1093/clinids/2.3.493 Published: 01 May 1980

Antiviral effect of guanidine and its derivatives. I. The inhibitory effect of guanidine on the multiplication of poliomyelitis virus in tissue culture.

Antiviral effect of guanidine and its derivatives. I. The inhibitory effect of guanidine on the multiplication of poliomyelitis virus in tissue culture.

Interference between influenza and poliomyelitis viruses in tissue culture.

In preliminary experiments it was shown that cells in monolayers of monkey kidney cultures can be protected from the cytopathogenic effect of poliomyelitis virus types 1, 2 and 3, some ECHO and Coxsackie viruses if influenza virus is added to the culture some days before the introduction of the challenge virus. The interference between influenza and poliomyelitis virus was then studied in detail. About 25% of the cells were degenerated by influenza virus alone. Most of the residual cells were protected against the degenerative effect of poliomyelitis virus when large amounts of influenza virus had been inoculated 48 hours before. If the interval between the virus inoculations was 12 hours only a small number of surviving cells were found. All cells degenerated when both viruses were inoculated simultaneously. No significant reduction in the yield of poliomyelitis virus was recorded when both viruses were inoculated simultaneously or when the interval between the two inoculations was less than 12 hours. With an interval of 12 hours the yield was reduced by 90%, and an interval of 72 hours resulted in a decrease of about 3 powers of ten in the propagation of poliomyelitis virus. Inoculation of influenza virus inactivated by heat or ultra-violet irradiation did not produce interference or cell protection. Impairment of the adsorption of the challenge virus was found not to be involved in the mechanism of the interference.

The present status of etiologic discovery in viral diseases.

Excerpt It is a distinguished honor to be invited to address this College, and in particular to be asked to deliver the Bruce Memorial Lecture in Preventive Medicine. I would take this opportunity ...

Interference and cell protection by poliomyelitis virus in tissue culture.

RECIPROCAL interference between strains of the three recognized types of poliomyelitis virus has been reported by Ledinko1, using roller-tube cultures of monkey testicular tissue. In her experiments, both the ‘interfering’ and the ‘excluded’ virus were fully cytopathogenic, and there was no suggestion of any mutual inhibition of their degenerative effects on the cells. Prevention of growth of the second virus, as shown by titration in the presence of type-specific antiserum against the first, was apparently the result of pre-emptive infection and subsequent destruction of susceptible cells by the first virus. The purpose of this communication is to describe a further example of interference among poliomyelitis viruses, in which a more direct recognition of the effect was made possible by the peculiar cytopathogenic behaviour of the interfering virus.

The growth of poliomyelitis virus in tissue culture. I. The use of a stationary bottle technique.

Australian Journal of Experimental Biology and Medical ScienceVolume 32, Issue 1 p. 23-28 Original Article THE GROWTH OF POLIOMYELITIS VIRUS IN TISSUE CULTURE I. THE USE OF A STATIONARY BOTTLE TECHNIQUE PL Bazeley, PL Bazeley Commonwealth Serum Laboratories, MelbourneSearch for more papers by this authorJR Thayer, JR Thayer Commonwealth Serum Laboratories, MelbourneSearch for more papers by this author PL Bazeley, PL Bazeley Commonwealth Serum Laboratories, MelbourneSearch for more papers by this authorJR Thayer, JR Thayer Commonwealth Serum Laboratories, MelbourneSearch for more papers by this author First published: 01 February 1954 https://doi.org/10.1038/icb.1954.2Citations: 3AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume32, Issue1February 1954Pages 23-28 Journal of the Australian and New Zealand Society for Immunology RelatedInformation

The growth of poliomyelitis virus in tissue culture. II. Isolation and typing of poliomyelitis virus strains using a stationary bottle technique.

Australian Journal of Experimental Biology and Medical ScienceVolume 32, Issue 1 p. 29-32 Original Article THE GROWTH OF POLIOMYELITIS VIRUS IN TISSUE CULTURE II. ISOLATION AND TYPING OF POLIOMYELITIS VIRUS STRAINS USING A STATIONARY BOTTLE TECHNIQUE PL Bazeley, PL Bazeley Commonwealth Serum Laboratories, MelbourneSearch for more papers by this authorJR Thayer, JR Thayer Commonwealth Serum Laboratories, MelbourneSearch for more papers by this author PL Bazeley, PL Bazeley Commonwealth Serum Laboratories, MelbourneSearch for more papers by this authorJR Thayer, JR Thayer Commonwealth Serum Laboratories, MelbourneSearch for more papers by this author First published: 01 February 1954 https://doi.org/10.1038/icb.1954.3Citations: 2AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Citing Literature Volume32, Issue1February 1954Pages 29-32 Journal of the Australian and New Zealand Society for Immunology RelatedInformation

Poliomyelitis virus in tissue culture. VI. Use of kidney epithelium grown on glass.

Summary1. Monkey kidney epithelial cells can be cultured on glass without a plasma clot. The kidney fragments are induced to adhere to the wall of the test tube by preheating of the tube (45°C), and partial drying after introduction of tissue. These cultures compare well with cultures prepared in plasma clots, and respond as readily to the introduction of poliomyelitis virus. A great advantage is realized in the simplicity of preparation of these cultures, and their incubation in stationary racks. Exclusive of preliminary preparations and subsequent stoppering of the tubes, two trained workers can prepare well over 1000 cultures in 1 hour. About 2000 such cultures can be provided from a single monkey. 2. Bottle cultures can be prepared by the same technic, and have yielded poliomyelitis virus titers of about 10-6 per 0.1 ml inoculum. Titers in tubes or bottles reach their maximum in 24 to 72 hours depending upon the dose of virus inoculated. 3. After a culture has grown to satisfactory dimensions, origina...

Inhibition of cytopathogenic effect of poliomyelitis viruses in tissue culture by antibiotic M-8450.

SummaryPretreatment of tissue cultured monkey testicular cells with antibiotic M-8450 inhibits the cytopathogenic effect of all 3 immunological types of poliomyelitis virus tested, but does not destroy or neutralize the viruses.

Poliomyelitis virus in tissue culture.

Poliomyelitis virus in tissue culture.

A Simplified Method for Cultivation of Poliomyelitis Virus in Tissue Culture

A Simplified Method for Cultivation of Poliomyelitis Virus in Tissue Culture

The cultivation of poliomyelitis virus in tissue culture of the human uterus, with emphasis on the broader aspects.

A historical background of the application of tissue culture technics to the laboratory study of poliomyelitis viruses is given. Tissue cultures are defined briefly and the two types usually applied to poliomyelitis virus studies described. Uses of the technics are outlined and further possible applications in poliomyelitis research suggested.

Cultivation of poliomyelitis virus in tissue culture. V. Observations on virus propagation in certain animal tissues with a synthetic nutrient medium.

Further observations have been made on the propagation of Lansing poliomyelitis virus in tissue cultures. It has been observed that tissues derived from several organs of rhesus monkeys will support virus growth in tissue cultures in Erlenmeyer flasks with a synthetic medium as the source of nutrient. Cultures of tissues from monkey testis, lung, kidney, and gut have survived for long periods, and virus has been regularly recovered even from fluids removed from cultures after as late as 125 days. Cultures of tissues from monkey brain and cord, and muscle, did not survive as long, and less virus was demonstrated in the supernatant fluids. Muscle from the diaphragm did not appear to support growth. Cultures of tissues from the brain, kidney, and lung of beef embryos survived for long periods, but no virus was found in any of the culture fluids.

Studies on the Cultivation of Poliomyelitis Viruses in Tissue Culture

Summary In 1949, in preliminary notes, we recorded the fact that the in vitro propagation of the poliomyelitis viruses may be accomplished in suspended cell cultures of various types of human tissues. The present paper details the procedures we have employed in the preparation and maintenance of suspended cell cultures for this purpose, and summarizes observations on the behavior of poliomyelitis viruses in such cultures, as observed during the past 4 years. Each of 3 antigenic types of poliomyelitis virus has been propagated in suspended cell cultures of human embryonic skin and muscle tissue, in cultures of human embryonic brain tissue and in cultures of mature human kidney tissue. In addition it has been demonstrated that one or more of these 3 types of virus will multiply in cultures of various other human embryonic tissues, including intestine, adrenal and spleen. Likewise, mature human tissues including thyroid, foreskin, and testis have been successfully employed for the cultivation of the Lansing strain as well as materials from two tumors, an embryoma of the kidney, and a neuroblastoma. Poliomyelitis virus has also been cultivated in monkey kidney cultures. Assay of the infectivity of materials removed from the tissue cultures was perfomred by the classical method of titration in animals and also by the technique of titration in vitro employing the cytopathogenic effect of the poliomyelitis viruses as an indicator of viral activity. Materials from cultures prepared with human embryonic skin-muscle tissues, kidney tissue, or brain tissues yielded the highest infectivity titers. Serial propagation in suspended cell cultures of human embryonic skin-muscle tissue was achieved for 23 passages with the Lansing strain, for a cumulate period of 331 days in cultivation, and for 15 passages with the Brunhilde strain, during a total period of 267 days. Throughout these prolonged periods of cultivation, virus production in each instance remained essentially constant as assayed by the in vitro technique. The titers as determined in vitro were in most cases equivalent to those observed in the central nervous system of the infected animal. However, in experiments with Lansing virus prolonged cultivation in human tissues was associated with a marked decline in apparent infectivity titer of the agent for the mouse. Likewise, in one experiment with Brunhilde virus, a significant decrease in the apparent infectivity titer for the monkey was observed.

General Preface to Studies on the Cultivation of Poliomyelitis Viruses in Tissue Culture

Abstract These remarks are designed as a preface to a series of reports on the propagation of the viruses of poliomyelitis in tissue culture. To achieve clarity in presentation, the division of topics has been somewhat arbitrary. In consequence each report will contain data obtained through the application of phenomena or techniques described in certain of the other papers. Accordingly, it was thought that it might prove helpful to the reader to summarize here the content of the various papers and to indicate their principal interrelationships. It also seemed appropriate to review in a preface of this sort the literature relevant to the series as a whole as well as the earlier communications from this laboratory. Since the demonstration by Landsteiner (1) in 1908 that poliomyelitis could be produced in monkeys, various workers have attempted to cultivate the causative agent in vitro.

Studies on the Cultivation of Poliomyelitis Viruses in Tissue Culture

Summary Evidence has been presented that the three prototype strains of poliomyelitis virus (Brunhilde, Lansing and Leon) can be propagated without difficulty in roller cultures of a variety of human tissues. They include embryonic skin-muscle and fascia, mature uterus and kidney. These three types of tissue have in our hands proved most useful, although multiplication of the Lansing strain occurs readily in cultures of mature human testis and prepuce. The Leon and Lansing viruses have likewise been cultivated in roller-tube cultures of kidney tissue from rhesus monkeys and the Lansing strain, in confirmation of the results of other investigators, in cultures of the testicular tissue of this species. The quantities of virus entering the fluid phase of the cultures approaches those encountered in the tissues of susceptible animals infected with these agents. In cultures composed of tissues from certain other mammalian species, embryonic and mature, no indication of viral multiplication has been observed. The procedures employed for the propagation of these agents in human tissues have been described in detail and the effect of certain modifications in technique on the growth of the virus has been determined. The advantages and disadvantages of the roller culture as compared with the suspended cell culture for the propagation of poliomyelitis viruses have been discussed and it is concluded that for most purposes the former is to be preferred.

Cultivation of poliomyelitis virus in tissue culture. III. Synthetic medium in roller tube cultures.

Summary1. The Brunhilde, Mahoney, Canadian Eskimo, Lansing, Y-SK, MEFl, Leon, and Saukett strains of poliomyelitis virus have been propagated in roller tube cultures of monkey testicular tissue treated with synthetic Mixture No. 199, devised by Morgan, Morton, and Parker. 2. Virus-induced cytopathogenic changes occurred in the fibroblasts and were similar to those observed in cultures treated with mixtures containing naturally occurring ingredients. 3. Virus and serum titrations in roller tube cultures were read 7 days after infection of the cultures; during this period no change of culture fluid was necessary. 4. The Brunhilde and Lansing strains were propagated in large roller tube cultures treated with Mixture 199, and high titers were obtained. 5. Culture fluids infected with Brunhilde and Lansing viruses from large roller tubes (mixed with adjuvants) were used to immunize groups of monkeys by the intramuscular route, and high serum antibody levels (4-0) developed promptly.

Pathogenesis of poliomyelitis.

SOME recent observations have suggested that it is time to review the evidence on the pathogenesis of poliomyelitis with a fresh point of view and especially to reexamine the rapidly weakening concept of poliomyelitis as a disease in which virus onlv invades and multiplies in nervous tissue. First of all, the work of Enders' group I in growing poliomyelitis virus in tissue culture has made it less difficult to accept the possibility that virus may multiply in non-nervous tissues. Second, the recent finding by several workers that antibody is already present in the serum of individuals at the time of onset of paralysis2-4 has led to a discounting of the many unsuccessful attempts to find virus in the blood of paralytic human cases,5 and has reopened the question of the occurrence of a viremia in the preparalytic period, such as occurs in other neurotropic virus diseases. In fact, the two reported isolations of virus from the blood of patients 5, 6 appear in the light of a rapid antibody response to support rather than to discount the possibility that viremia may be a regular occurrence early in the disease, especially since in one instance the virus was isolated not more than six hours after onset of an abortive illness.5 The isolation of virus in the blood stream of cynomolgus monkeys and of chimpanzees in the incubation period after

The Influence of Chemicals on the Propagation of Poliomyelitis Virus in Tissue Culture

Summary Various compounds have been tested for their ability to inhibit the propagation of poliomyelitis virus in tissue culture. Five of nine analogues of amino acids, cysteic acid, dl-ethionine, N-dichloroacetyl-α-(p-nitrophenyl) glycine, α-amino-β-phenylethane sulfonic acid, and β-2-thienylalanine were found to inhibit viral growth. Benzimidazole, 2,6-diaminopurine, and proflavin, all compounds involved in nucleic acid synthesis, were also effective inhibitors. The vitamin analogues as a group were ineffective, but one of these, dl-homobiotin, was found to be active. Glycerol monoacetin, an antagonist of fluoroacetate and phagopedin sigma, an antibiotic, were also found to be inhibitory. The specificity of action of two analogues of amino acids, ethionine and β-2-thienylalanine, and of two metabolic analogues of purines, benzimidazole and 2,6-diaminopurine, was shown by the partial reversal of their inhibitory effect with the appropriate metabolites. These metabolites, d-methionine, dlphenylalanine, adenine, guanine, and uracil are therefore shown to be essential for the growth of poliomyelitis virus in tissue culture.