scholarly journals STUDIES ON VARIANTS OF POLIOMYELITIS VIRUS

1954 ◽  
Vol 99 (6) ◽  
pp. 551-576 ◽  
Author(s):  
Albert B. Sabin ◽  
Walter A. Hennessen ◽  
Johan Winsser
Keyword(s):  
Spinal Cord ◽  
Kidney Tissue ◽  
Intracerebral Injection ◽  
Cynomolgus Monkeys ◽  
Poliomyelitis Virus ◽  
Virulent Strains ◽  
Motor Neurones ◽  
Type 3

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 to cynomolgus monkeys indicated that mere propagation in cultures of kidney tissue of cynomolgus 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 in cynomolgus 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 in cynomolgus 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 of cynomolgus monkeys when these are directly exposed to them by accidental intraneural or traumatic intracerebral injection. On propagation in cynomolgus kidney cultures the modified viruses reached titers of approximately 107 TCD50 per ml., as measured by cytopathogenic activity on renal epithelial cells in vitro, yet produced no perceptible pathologic changes in the muscles, kidneys, testes, ovaries, heart, pancreas, adrenals, liver, or spleen of cynomolgus monkeys inoculated intramuscularly. The modified viruses were immunogenic after intramuscular injection, but a large proportion of cynomolgus 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 for cynomolgus 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 for cynomolgus monkeys, and retained its paralytogenic activity in intraspinally inoculated mice after it had lost its virulence for cynomolgus monkeys by the indicated routes. The parent Type 3 virus was paralytogenic in intraspinally inoculated mice when it was still fully virulent for cynomolgus monkeys, but this property disappeared in the modified virus when it became avirulent for monkeys.

POLIOMYELITIS IN CANADIAN ESKIMOS: LABORATORY STUDIES. V. TYPE 1 AND TYPE 3 POLIOMYELITIS ANTIBODY LEVELS IN BAFFIN ISLAND ESKIMOS

1954 ◽  
Vol 32 (1) ◽  
pp. 119-125
Author(s):  
W. Wood ◽  
Eina M. Clark ◽  
F. T. Shimada ◽  
A. J. Rhodes
Keyword(s):  
Medical Records ◽  
Baffin Island ◽  
Tissue Cultures ◽  
Laboratory Studies ◽  
Poliomyelitis Virus ◽  
Antibody Titers ◽  
Antibody Levels ◽  
Type 3

Studies on the basic immunology of poliomyelitis in Canadian Eskimos have been continued. Some 87 sera collected from Eskimos at Pangnirtung, Baffin Island, have been examined for the presence of Type 1 and Type 3 poliomyelitis antibody by quantitative tests in tissue cultures. The same sera were previously examined for Type 2 antibody by quantitative tests in mice. The results of the three determinations are now presented together for comparison. These sera came from Eskimos aged 2 to 72 years of age. None of the Eskimos showed any evidence of paralysis. Examination of the medical records did not suggest that any paralytic disease had been present in this part of Baffin Island. Very few of the sera showed the presence of poliomyelitis antibody; thus, Type 1 antibody was demonstrated in the sera of 8%, Type 2 antibody in the sera of 9%, and Type 3 antibody in the sera of 14%. No significant number of Eskimos below the age of 45 years had acquired poliomyelitis antibody. The antibody titers mostly ranged between 10−1.0 and 10−2.0, and were significantly lower than the titers customarily found in recently paralyzed cases. These findings suggest that poliomyelitis infection occurred in Pangnirtung Eskimos many years before the date on which the samples were taken (1951). These results point to the worldwide prevalence of the three types of poliomyelitis virus.

CLINICAL TRIALS IN INFANTS OF ORALLY ADMINISTERED ATTENUATED POLIOMYELITIS VIRUSES

PEDIATRICS ◽  
1959 ◽  
Vol 23 (6) ◽  
pp. 1041-1062
Author(s):  
Stanley Alan Plotkin ◽  
Hilary Koprowski ◽  
Joseph Stokes
Keyword(s):  
Clinical Trials ◽  
Fecal Excretion ◽  
Jackson Type ◽  
Poliomyelitis Virus ◽  
Minor Illness ◽  
The Difference ◽  
Antibody Levels ◽  
Type 3

Forty-six infants, ranging from less than 1 day to 6 months of age, were given more than 100 feedings of living, attenuated poliomyelitis viruses without the occurrence of major or minor illness. The strains used were CHAT (type 1), Wistar (type 1), Jackson (type 2), P-712 (type 2) and Fox (type 3). All strains except the Jackson strain were found to be antigenic on oral administration. Response to vaccination was demonstrated in these infants by the presence after vaccination of antibody levels significantly in excess of those attributable to transplacentally acquired antibodies, and by the detection of fecal excretion of poliomyelitis virus. Infants less than 2 months old were more difficult to immunize than older infants. The evidence suggests that biologic immaturity rather than transplacental antibodies caused the difference. When the three types of poliomyelitis virus were fed at 3-week intervals, responses occurred to all types. No interference between types was observed when they were fed in all possible sequences. Three infants given a second feeding of homotypic, attenuated poliomyelitis virus 3 to 5 months after a successful vaccination showed resistance to intestinal reinfection.

scholarly journals AN ALUMINUM MARKER FOR THE DIFFERENTIATION AND SEPARATION OF VIRULENT AND ATTENUATED POLIOVIRUSES

1962 ◽  
Vol 115 (4) ◽  
pp. 763-775 ◽  
Author(s):  
Craig Wallis ◽  
Joseph L. Melnick ◽  
George D. Ferry ◽  
Ira L. Wimberly
Keyword(s):  
Thermal Inactivation ◽  
Genetic Changes ◽  
Virulent Strains ◽  
Virulent Type ◽  
Type 3

A new character, the A marker, for polioviruses is described. In the presence of Al+++ (1 to 100 mM) attenuated, but not virulent, strains of type 1 and type 2 polioviruses are stabilized so that they resist thermal inactivation at 50°C. Differences between the attenuated and virulent type 3 strains studied were of the opposite character and less marked. By the use of optimal concentrations of Al+++ (12 mM for type 1 and 1 mM for type 2) attenuated strains can be separated from mixtures containing virulent type 1 or 2 strains. The A marker was found to be correlated with the d but not the rct/40 or T marker. The A marker has been used for following genetic changes of vaccine strains after their multiplication in man.

POLIOMYELITIS IN CANADIAN ESKIMOS: LABORATORY STUDIES. V. TYPE 1 AND TYPE 3 POLIOMYELITIS ANTIBODY LEVELS IN BAFFIN ISLAND ESKIMOS

1954 ◽  
Vol 32 (2) ◽  
pp. 119-125
Author(s):  
W. Wood ◽  
Eina M. Clark ◽  
F. T. Shimada ◽  
A. J. Rhodes
Keyword(s):  
Medical Records ◽  
Baffin Island ◽  
Tissue Cultures ◽  
Laboratory Studies ◽  
Poliomyelitis Virus ◽  
Antibody Titers ◽  
Antibody Levels ◽  
Type 3

Studies on the basic immunology of poliomyelitis in Canadian Eskimos have been continued. Some 87 sera collected from Eskimos at Pangnirtung, Baffin Island, have been examined for the presence of Type 1 and Type 3 poliomyelitis antibody by quantitative tests in tissue cultures. The same sera were previously examined for Type 2 antibody by quantitative tests in mice. The results of the three determinations are now presented together for comparison. These sera came from Eskimos aged 2 to 72 years of age. None of the Eskimos showed any evidence of paralysis. Examination of the medical records did not suggest that any paralytic disease had been present in this part of Baffin Island. Very few of the sera showed the presence of poliomyelitis antibody; thus, Type 1 antibody was demonstrated in the sera of 8%, Type 2 antibody in the sera of 9%, and Type 3 antibody in the sera of 14%. No significant number of Eskimos below the age of 45 years had acquired poliomyelitis antibody. The antibody titers mostly ranged between 10−1.0 and 10−2.0, and were significantly lower than the titers customarily found in recently paralyzed cases. These findings suggest that poliomyelitis infection occurred in Pangnirtung Eskimos many years before the date on which the samples were taken (1951). These results point to the worldwide prevalence of the three types of poliomyelitis virus.

Partial resialylation of human asialotransferrin types 1 and 2 in the rat

1984 ◽  
Vol 62 (9) ◽  
pp. 853-858 ◽  
Author(s):  
Erwin Regoeczi ◽  
Paul A. Chindemi ◽  
Maria T. Debanne
Keyword(s):  
Sialic Acid ◽  
Electrophoretic Mobility ◽  
Acid Content ◽  
Sialic Acid Content ◽  
Small Doses ◽  
Type 3 ◽  
Time Type

125I-labeled asialotransferrin types 1 and 2 were administered in small doses to rats. The protein still in the plasma after 1–12 h was partially repurified and electrophoresed at pH 8.1, together with a transferrin standard that is composed of all six forms of the protein with respect to sialic acid content. The electrophoretic mobility of both asialotransferrins increased with time, type 2 being affected sooner than type 1. The changed mobility was due to increased electronegativity that was fully reversible by treatment of the samples with neuraminidase, thus identifying the underlying cause as partial resialylation. Asialotransferrin incubated in vitro with serum, plasma, or whole blood for 16 h exhibited no change in electrophoretic mobility. In conjunction with an earlier study on asialotransferrin type 3, it was found that the apparent speeds of resialylation of the three asialotransferrins were in the same order as their affinities for the asialoglycoprotein-binding hepatic lectin. This suggests the involvement of an endo- rather than of an ecto-transferase. Transfer of 59Fe from asialotransferrins to the liver was used to monitor the frequency of hepatocyte–asialotransferrin interactions. Iron deposition in the liver took place much more rapidly than the appearance of detectable quantities of partially resialylated asialotransferrin molecules in the circulation. It is concluded that each asialotransferrin molecule probably undergoes several passages through the hepatocyte before its glycans become modified.

scholarly journals TRIM5 genotypes in cynomolgus monkeys primarily influence inter-individual diversity in susceptibility to monkey-tropic human immunodeficiency virus type 1

2013 ◽  
Vol 94 (6) ◽  
pp. 1318-1324 ◽  
Author(s):  
Akatsuki Saito ◽  
Masako Nomaguchi ◽  
Ken Kono ◽  
Yasumasa Iwatani ◽  
Masaru Yokoyama ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Cynomolgus Monkeys ◽  
Gene Variation ◽  
Immunodeficiency Virus ◽  
Hiv 1

TRIM5α restricts human immunodeficiency virus type 1 (HIV-1) infection in cynomolgus monkey (CM) cells. We previously reported that a TRIMCyp allele expressing TRIM5–cyclophilin A fusion protein was frequently found in CMs. Here, we examined the influence of TRIM5 gene variation on the susceptibility of CMs to a monkey-tropic HIV-1 derivative (HIV-1mt) and found that TRIMCyp homozygotes were highly susceptible to HIV-1mt not only in vitro but also in vivo. These results provide important insights into the inter-individual differences in susceptibility of macaques to HIV-1mt.

scholarly journals Genetic and Biochemical Studies of Polioviruscis-Acting Replication Element cre in Relation to VPg Uridylylation

2000 ◽  
Vol 74 (22) ◽  
pp. 10371-10380 ◽  
Author(s):  
Elizabeth Rieder ◽  
Aniko V. Paul ◽  
Dong Wook Kim ◽  
Jacques H. van Boom ◽  
Eckard Wimmer
Keyword(s):  
Genome Replication ◽  
Coding Region ◽  
Stem Loop ◽  
Genetic Changes ◽  
Poliovirus Type ◽  
Type 3 ◽  
Type Sequence

ABSTRACT In addition to highly conserved stem-loop structures located in the 5′- and 3′-nontranslated regions, genome replication of picornaviruses requires cis-acting RNA elements located in the coding region (termed cre) (K. L. McKnight and S. M. Lemon, J. Virol. 70:1941–1952, 1996; P. E. Lobert, N. Escriou, J. Ruelle, and T. Michiels, Proc. Natl. Acad. Sci. USA 96:11560–11565, 1999; I. Goodfellow, Y. Chaudhry, A. Richardson, J. Meredith, J. W. Almond, W. Barclay, and D. J. Evans, J. Virol. 74:4590–4600, 2000). cre elements appear to be essential for minus-strand RNA synthesis by an as-yet-unknown mechanism. We have discovered that the cre element of poliovirus (mapping to the 2C coding region of poliovirus type 1; nucleotides 4444 to 4505 in 2C), which is homologous to thecre element of poliovirus type 3, is preferentially used as a template for the in vitro uridylylation of VPg catalyzed by 3Dpol in a reaction that is greatly stimulated by 3CDpro (A. V. Paul, E. Rieder, D. W. Kim, J. H. van Boom, and E. Wimmer, J. Virol. 74:10359–10370, 2000). Here we report a direct correlation between mutations that eliminate, or severely reduce, the in vitro VPg-uridylylation reaction and produce replication phenotypes in vivo. None of the genetic changes significantly influenced translation or polyprotein processing. A substitution mapping to the first A (A4472C) of a conservedAAACA sequence in the loop of PV-cre(2C) eliminated the ability of the cre RNA to serve as template for VPg uridylylation and abolished RNA infectivity. Mutagenesis of the second A (A4473C; AAACA) severely reduced the yield of VPgpUpU and RNA infectivity was restored only after reversion to the wild-type sequence. The effect of substitution of the third A (A4474G; AAACA) was less severe but reduced both VPg uridylylation and virus yield. Disruption of base pairing within the upper stem region of PV-cre(2C) also affected uridylylation of VPg. Virus derived from transcripts containing mutations in the stem was either viable or quasi-infectious.

scholarly journals Ovicidal activity of different concentrations of Pochonia chlamydosporia chlamydospores on Taenia taeniaeformis eggs

2010 ◽  
Vol 85 (1) ◽  
pp. 7-11 ◽  
Author(s):  
F.R. Braga ◽  
A.R. Silva ◽  
R.O. Carvalho ◽  
J.V. Araújo ◽  
P.S.A. Pinto
Keyword(s):  
Biological Control Agent ◽  
Petri Dish ◽  
Control Agent ◽  
Control Group ◽  
Ovicidal Activity ◽  
Pochonia Chlamydosporia ◽  
Taenia Taeniaeformis ◽  
Type 3

AbstractThree concentrations of chlamydospores of the nematophagous fungus Pochonia chlamydosporia (1000, 10,000 and 20,000 per Petri dish) were evaluated in vitro on Taenia taeniaeformis eggs. Chlamydospores at each concentration were cultured in two different media: 2% water-agar (2%WA) and 2% corn-meal-agar (2%CMA). Taenia taeniaeformis eggs were plated in each chlamydospore concentration in 2%WA and 2%CMA (treated groups) and without fungus (control group). Eggs were removed from each Petri dish at intervals of 7, 14 and 21 days and classified according to ovicidal activity (type 1, type 2 and type 3 effects). Plates containing 2%CMA showed the highest percentages for type 3 effect (81.3%) on the 21st day of observation. A difference (P < 0.01) between the media 2%WA and 2%CMA for type 1 effect was observed only at a concentration of 1000 chlamydospores on the 7th day. There were differences (P < 0.01) between 2%WA and 2%CMA on the 14th and 21st days, at the concentration of 20,000 chlamydospores, for type 1 and type 3 effects. Regression curves for type 3 effect in 2%WA and 2%CMA at the tested concentrations showed higher ovicidal activity with increasing chlamydospore concentrations. Results indicate that, at concentrations of 1000, 10,000 and 20,000 per Petri dish, chlamydospores of P. chlamydosporia effectively destroyed T. taeniaeformis eggs and can be considered a potential biological control agent for this cestode.

scholarly journals A comparison of complement-fixation titres in poliomyelitis-infected tissue-culture fluids and mouse brains

1958 ◽  
Vol 56 (2) ◽  
pp. 254-259 ◽  
Author(s):  
Golda Selzer
Keyword(s):  
Tissue Culture ◽  
Technical Assistance ◽  
Complement Fixation ◽  
Kidney Tissue ◽  
The Other ◽  
Soluble Antigen ◽  
Infective Virus ◽  
Suckling Mouse ◽  
Poliomyelitis Virus

Ultra-centrifugation of emulsions from suckling mouse brains infected with the MEF1 strain of poliomyelitis virus separates a non-infective antigen, or soluble antigen, from infective virus. This antigen is responsible for most of the complement fixation and explains the high titres obtained. On the other hand, the same virus, and also Mahoney, Type 1 poliomyelitis virus, grown in monkey kidney tissue culture, fail to produce this soluble antigen, and this is probably a factor in the low complement-fixing titres obtained in tests with these fluids.The author would like to express her appreciation of Miss M. Butchart's valuable technical assistance.

Il-1β and prostaglandin E2 attenuate the hypercapnic as well as the hypoxic respiratory response via prostaglandin E receptor type 3 in neonatal mice

2014 ◽  
Vol 117 (9) ◽  
pp. 1027-1036 ◽  
Author(s):  
Veronica Siljehav ◽  
Yuri Shvarev ◽  
Eric Herlenius
Keyword(s):  
Spinal Cord ◽  
Brain Stem ◽  
Receptor Type ◽  
Severe Hypoxia ◽  
Hypoxic Exposure ◽  
Prostaglandin E ◽  
Respiratory Response ◽  
En Bloc ◽  
Type 3

Prostaglandin E2 (PGE2) serves as a critical mediator of hypoxia, infection, and apnea in term and preterm babies. We hypothesized that the prostaglandin E receptor type 3 (EP3R) is the receptor responsible for PGE2-induced apneas. Plethysmographic recordings revealed that IL-1β (ip) attenuated the hypercapnic response in C57BL/6J wild-type (WT) but not in neonatal (P9) EP3R−/− mice ( P < 0.05). The hypercapnic responses in brain stem spinal cord en bloc preparations also differed depending on EP3R expression whereby the response was attenuated in EP3R−/− preparations ( P < 0.05). After severe hypoxic exposure in vivo, IL-1β prolonged time to autoresuscitation in WT but not in EP3R−/− mice. Moreover, during severe hypoxic stress EP3R−/− mice had an increased gasping duration ( P < 0.01) as well as number of gasps ( P < 0.01), irrespective of intraperitoneal treatment, compared with WT mice. Furthermore, EP3R−/− mice exhibited longer hyperpneic breathing efforts when exposed to severe hypoxia ( P < 0.01). This was then followed by a longer period of secondary apnea before autoresuscitation occurred in EP3R−/− mice ( P < 0.05). In vitro, EP3R−/− brain stem spinal cord preparations had a prolonged respiratory burst activity during severe hypoxia accompanied by a prolonged neuronal arrest during recovery in oxygenated medium ( P < 0.05). In conclusion, PGE2 exerts its effects on respiration via EP3R activation that attenuates the respiratory response to hypercapnia as well as severe hypoxia. Modulation of the EP3R may serve as a potential therapeutic target for treatment of inflammatory and hypoxic-induced detrimental apneas and respiratory disorders in neonates.

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