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STUDIES ON VARIANTS OF POLIOMYELITIS VIRUS

I. EXPERIMENTAL SEGREGATION AND PROPERTIES OF AVIRULENT VARIANTS OF THREE IMMUNOLOGIC TYPES

Albert B Sabin1,Walter A Hennessen1,Johan Winsser1
1From The Children's Hospital Research Foundation, University of Cincinnati College of Medicine, Cincinnati

Received 1954 Feb 4.

Copyright © Copyright, 1954, by The Rockefeller Institute for Medical Research New York

This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (seehttp://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described athttp://creativecommons.org/licenses/by-nc-sa/4.0/).

PMCID: PMC2136347  PMID:13163327

Abstract

Attempts were made to "convert" highly virulent strains of the 3 immunologic types of poliomyelitis virus (Mahoney, Y-SK, and Leon) into avirulent variants. Tests involving intracerebral, intramuscular, or oral administration of virus tocynomolgus monkeys indicated that mere propagation in cultures of kidney tissue ofcynomolgus monkeys had no effect on virulence when single or small numbers of virus particles were used as seed, and harvests were delayed for 24 hours or more after the appearance of cytopathogenic change. On the other hand, passages at 24 hour intervals with large inocula (105 to 106 TCD60) produced culture fluids with diminished virulence and unusual patterns of response incynomolgus monkeys. Purification of such culture fluids by the terminal dilution technique yielded modified strains which proved to be avirulent after administration by the intracerebral, intramuscular, or oral routes incynomolgus monkeys. Neither paralysis nor CNS lesions were found in any of more than 80 monkeys inoculated intracerebrally with various amounts of virus. However, focal neuronal lesions were found in the spinal cord of 3 of 48 monkeys inoculated intramuscularly with various amounts of the Mahoney variant, in 2 of 20 receiving the Y-SK variant, though in none of 40 inoculated with various amounts of the Leon variant. Virus recovered from the spinal cord of one of the monkeys in the Mahoney group produced no paralysis on intracerebral passage in monkeys. It is assumed that all 3 modified viruses possess a limited capacity to affect lower motor neurones ofcynomolgus monkeys when these are directly exposed to them by accidental intraneural or traumatic intracerebral injection. On propagation incynomolgus kidney cultures the modified viruses reached titers of approximately 107 TCD50 per ml., as measured by cytopathogenic activity on renal epithelial cellsin vitro, yet produced no perceptible pathologic changes in the muscles, kidneys, testes, ovaries, heart, pancreas, adrenals, liver, or spleen ofcynomolgus monkeys inoculated intramuscularly. The modified viruses were immunogenic after intramuscular injection, but a large proportion ofcynomolgus monkeys failed to develop antibody after small doses, indicating that in this host the experimentally produced variants multiplied less readily in non-nervous tissue than the virulent parent strains. Tests with the Type 1 virus showed that the orally administered avirulent variant can induce the formation of antibody and bring about resistance to the occurrence of paralysis such as results from ingestion of the virulent, parent strain. The Types 1 and 2 modified viruses are paralytogenic in mice after direct spinal inoculation whereas the Type 3 virus is not. The Type 1 virus became paralytogenic for mice when it lost its virulence forcynomolgus monkeys by the indicated routes. The Type 2 virus lost its virulence for mice by the intracerebral but not intraspinal routes when it was still fully virulent forcynomolgus monkeys, and retained its paralytogenic activity in intraspinally inoculated mice after it had lost its virulence forcynomolgus monkeys by the indicated routes. The parent Type 3 virus was paralytogenic in intraspinally inoculated mice when it was still fully virulent forcynomolgus monkeys, but this property disappeared in the modified virus when it became avirulent for monkeys.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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Articles from The Journal of Experimental Medicine are provided here courtesy ofThe Rockefeller University Press

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