Effects of Vaccine Strain Mutations in Domain V of the Internal Ribosome Entry Segment Compared in the Wild Type Poliovirus Type 1 Context

ABSTRACT The emergence of circulating vaccine-derived poliovirus (cVDPV) strains in suboptimally vaccinated populations is a serious threat to the global poliovirus eradication. The genetic determinants for the transmissibility phenotype of polioviruses, and in particularly of cVDPV strains, are currently unknown. Here we describe the fecal excretion of wild-type poliovirus, oral polio vaccine, and cVDPV (Hispaniola) strains after intraperitoneal injection in poliovirus receptor-transgenic mice. Both the pattern and the level of fecal excretion of the cVDPV strains resemble those of wild-type poliovirus type 1. In contrast, very little poliovirus was present in the feces after oral polio vaccine administration. This mouse model will be helpful in elucidating the genetic determinants for the high fecal-oral transmission phenotype of cVDPV strains.

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Poliovirus Internal Ribosome Entry Segment Structure Alterations That Specifically Affect Function in Neuronal Cells: Molecular Genetic Analysis

Journal of Virology ◽

10.1128/jvi.76.21.10617-10626.2002 ◽

2002 ◽

Vol 76 (21) ◽

pp. 10617-10626 ◽

Cited By ~ 37

Author(s):

Cécile E. Malnou ◽

Tuija A. A. Pöyry ◽

Richard J. Jackson ◽

Katherine M. Kean

Keyword(s):

Secondary Structure ◽

Neuronal Cells ◽

Neuronal Cell ◽

In Vitro Translation ◽

Internal Ribosome Entry ◽

Cell Extracts ◽

Internal Ribosome Entry Segment ◽

Domain V ◽

Bulge Loop

ABSTRACT Translation of poliovirus RNA is driven by an internal ribosome entry segment (IRES) present in the 5′ noncoding region of the genomic RNA. This IRES is structured into several domains, including domain V, which contains a large lateral bulge-loop whose predicted secondary structure is unclear. The primary sequence of this bulge-loop is strongly conserved within enteroviruses and rhinoviruses: it encompasses two GNAA motifs which could participate in intrabulge base pairing or (in one case) could be presented as a GNRA tetraloop. We have begun to address the question of the significance of the sequence conservation observed among enterovirus reference strains and field isolates by using a comprehensive site-directed mutagenesis program targeted to these two GNAA motifs. Mutants were analyzed functionally in terms of (i) viability and growth kinetics in both HeLa and neuronal cell lines, (ii) structural analyses by biochemical probing of the RNA, and (iii) translation initiation efficiencies in vitro in rabbit reticulocyte lysates supplemented with HeLa or neuronal cell extracts. Phenotypic analyses showed that only viruses with both GNAA motifs destroyed were significantly affected in their growth capacities, which correlated with in vitro translation defects. The phenotypic defects were strongly exacerbated in neuronal cells, where a temperature-sensitive phenotype could be revealed at between 37 and 39.5°C. Biochemical probing of mutated domain V, compared to the wild type, demonstrated that such mutations lead to significant structural perturbations. Interestingly, revertant viruses possessed compensatory mutations which were distant from the primary mutations in terms of sequence and secondary structure, suggesting that intradomain tertiary interactions could exist within domain V of the IRES.

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Effect of Mutations in the Human Immunoglobulin A1 (IgA1) Hinge on Its Susceptibility to Cleavage by Diverse Bacterial IgA1 Proteases

Infection and Immunity ◽

10.1128/iai.73.3.1515-1522.2005 ◽

2005 ◽

Vol 73 (3) ◽

pp. 1515-1522 ◽

Cited By ~ 29

Author(s):

Bernard W. Senior ◽

Jenny M. Woof

Keyword(s):

Peptide Bond ◽

Human Immunoglobulin ◽

Peptide Sequence ◽

Wild Type ◽

Peptide Bonds ◽

Streptococcus Sanguis ◽

In The Wild ◽

Scissile Bond ◽

Cleavable Peptide

ABSTRACT Components of the human immunoglobulin A1 (IgA1) hinge governing sensitivity to cleavage by bacterial IgA1 proteases were investigated. Recombinant antibodies with distinct hinge mutations were constructed from a hybrid comprised of human IgA2 bearing half of the human IgA1 hinge region. This hybrid antibody and all the mutant antibodies derived from it were resistant to cleavage by the IgA1 proteases from Streptococcus oralis and Streptococcus mitis biovar 1 strains but were cleaved to various degrees by those of Streptococcus pneumoniae, some Streptococcus sanguis strains, and the type 1 and 2 IgA1 proteases of Haemophilus influenzae, Neisseria meningitidis, and Neisseria gonorrhoeae. Remarkably, those proteases that cleave a Pro-Ser peptide bond in the wild-type IgA1 hinge were able to cleave mutant antibodies lacking a Pro-Ser peptide bond in the hinge, and those that cleave a Pro-Thr peptide bond in the wild-type IgA1 hinge were able to cleave mutant antibodies devoid of a Pro-Thr peptide bond in the hinge. Thus, the enzymes can cleave alternatives to their preferred postproline peptide bond when such a bond is unavailable. Peptide sequence analysis of a representative antibody digestion product confirmed this conclusion. The presence of a cleavable peptide bond near the CH2 end of the hinge appeared to result in greater cleavage than if the scissile bond was at the CH1 end of the hinge. Proline-to-serine substitution at residue 230 in a hinge containing potentially cleavable Pro-Ser and Pro-Thr peptide bonds increased the resistance of the antibody to cleavage by many IgA1 proteases.

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Sabin attenuated LSc/2ab strain of poliovirus spreads to the spinal cord from a peripheral nerve in bonnet monkeys (Macaca radiata)

Journal of General Virology ◽

10.1099/0022-1317-82-6-1329 ◽

2001 ◽

Vol 82 (6) ◽

pp. 1329-1338 ◽

Cited By ~ 2

Author(s):

Esther M. Ponnuraj ◽

T. Jacob John ◽

Myron J. Levin ◽

Eric A. F. Simoes

Keyword(s):

Spinal Cord ◽

Ulnar Nerve ◽

Neuronal Loss ◽

Viral Rna ◽

Paralytic Poliomyelitis ◽

Cns Infection ◽

Wild Type ◽

Spinal Cord Neurons ◽

Poliovirus Type

Vaccine-associated paralytic poliomyelitis is a serious concern while using the live attenuated oral polio vaccine for the eradication of poliomyelitis. The bonnet monkey model of poliovirus central nervous system (CNS) infection following experimental inoculation into the ulnar nerve allows the comparative study of wild-type and attenuated poliovirus invasiveness. Dosages ⩾104 TCID50 of Mahoney strain of poliovirus type 1 [PV1(M)] result in paralysis. In contrast, even with 107 TCID50 of Sabin attenuated strain of poliovirus type 1 (LSc/2ab), no paralysis occurs, but virus spreads into the CNS where viral RNA is found in spinal cord neurons. While wild-type PV1(M) viral RNA replicates in neurons (and possibly in glial cells) and in cells around vessel walls, which may be mononuclear or endothelial cells, attenuated viral RNA is detected only in neurons. Systemic viraemia and gastrointestinal virus shedding occurs only in PV1(M)-infected animals. While a systemic serologic response is detected in both groups of animals, cerebrospinal fluid antibodies are detected only in animals infected with PV1(M). Both the PV1(M) and LSc/2ab strains spread to the cervical spinal cord and then to the lumbar spinal cord following ulnar nerve inoculation. Neuronophagia and neuronal loss are only seen in PV1(M)-infected monkeys in whom clinical paralysis is observed. Infection with LSc/2ab does not result in neuronophagia, neuronal loss or clinical paralysis. Spread of attenuated poliovirus in spinal cord neurons without causing paralysis following inoculation into the ulnar nerve is an important finding.

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Effects of the Sabin-like mutations in domain V of the internal ribosome entry segment on translational efficiency of the Coxsackievirus B3

Molecular Genetics and Genomics ◽

10.1007/s00438-006-0155-3 ◽

2006 ◽

Vol 276 (4) ◽

pp. 402-412 ◽

Cited By ~ 11

Author(s):

Manel Ben M’hadheb-Gharbi ◽

Jawhar Gharbi ◽

Sylvie Paulous ◽

Michèle Brocard ◽

Anastasia Komaromva ◽

...

Keyword(s):

Coxsackievirus B3 ◽

Translational Efficiency ◽

Internal Ribosome Entry ◽

Internal Ribosome Entry Segment ◽

Domain V

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Ficolin B in Diabetic Kidney Disease in a Mouse Model of Type 1 Diabetes

Mediators of Inflammation ◽

10.1155/2015/653260 ◽

2015 ◽

Vol 2015 ◽

pp. 1-6 ◽

Cited By ~ 2

Author(s):

Charlotte Berg Holt ◽

Jakob Appel Østergaard ◽

Esben Axelgaard ◽

Gitte Krogh Nielsen ◽

Yuichi Endo ◽

...

Keyword(s):

Knockout Mice ◽

Diabetic Mice ◽

Wild Type ◽

Renal Hypertrophy ◽

Kidney Weight ◽

Diabetic Kidney ◽

In The Wild ◽

The Difference ◽

Mannan Binding Lectin

Background.The innate immune system may have adverse effects in diabetes and cardiovascular disease. The complement system seems to play a key role through erroneous complement activation via hyperglycaemia-induced neoepitopes. Recently mannan-binding lectin (MBL) was shown to worsen diabetic kidney changes. We hypothesize that mouse ficolin B exerts detrimental effects in the diabetic kidney as seen for MBL.Methods.We induced diabetes with streptozotocin in female wild-type mice and ficolin B knockout mice and included two similar nondiabetic groups. Renal hypertrophy and excretion of urinary albumin and creatinine were quantified to assess diabetic kidney damage.Results.In the wild-type groups, the kidney weighed 24% more in the diabetic mice compared to the controls. The diabetes-induced increase in kidney weight was 29% in the ficolin B knockout mice, that is, equal to wild-type animals (two-way ANOVA,P=0.60). In the wild-type mice the albumin-to-creatinine ratio (ACR) was 32.5 mg/g higher in the diabetic mice compared to the controls. The difference was 62.5 mg/g in the ficolin B knockout mice, but this was not significantly different from the wild-type animals (two-way ANOVA,P=0.21).Conclusions.In conclusion, the diabetes-induced effects on kidney weight and ACR were not modified by the presence or absence of ficolin B.

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Vaccine-Preventable Diseases

Tutorial Topics in Infection for the Combined Infection Training Programme ◽

10.1093/oso/9780198801740.003.0024 ◽

2019 ◽

Author(s):

C. Y. William Tong

Keyword(s):

Measles Virus ◽

Oral Vaccine ◽

Wild Type ◽

Live Attenuated Vaccine ◽

Poliovirus Type ◽

The World ◽

Global Eradication ◽

One Year ◽

Health Organization

These are diseases in which an effective preventive vaccine exists. A death that could have been prevented by vaccination is a vaccine- preventable death. The World Health Organization (WHO) has identified twenty-five diseases as vaccine preventable. This list may expand as new vaccines are being developed. The Expanded Programme on Immunization, or EPI, is vaccination programme introduced in 1974 by the WHO to all nations. The EPI initially targeted diphtheria, whooping cough, tetanus, measles, poliomyelitis, and tuberculosis. The aim was to provide universal immunization for all children by 1990 and to achieve health for all by 2000. In 2010, about 85% of children under one year of age in the world had received at least three doses of DTP vaccine (diphtheria, tetanus, and polio). Additional vaccines have now been added to the original six targets. Most countries have now added Hepatitis B (not in UK) and Haemophilus influenzae type b (Hib) to their routine infant immunization schedules, and an increasing number are in the process of adding pneumococcal conjugate vaccine and rotavirus vaccines to their schedules. Immunization is a proven tool for controlling and even eradicating infectious diseases. The immunization campaign against smallpox between 1967 and 1977 resulted in the eradication of smallpox. Apart from smallpox, the only other viral infection that was declared eradicated through vaccination campaign was rinderpest in cattle (2011), a close relative of measles virus in humans. Another major infection target for global eradication is against poliomyelitis—the global polio eradication initiative (GPEI). When the programme began in 1988, polio threatened 60% of the world’s population. Eradication of poliomyelitis is now within reach: infections have fallen by 99%; wild type polio type 2 was last detected in 1999 and declared eradicated in 2015; wild-type poliovirus type 3 has not been detected in the world since 2012. Poliovirus type 1 is the only wild- type virus in circulation and endemic transmission is only reported in Afghanistan and Pakistan. Currently, the old trivalent oral poliovirus vaccine is replaced by the more potent bivalent poliovirus type 1 and 3 vaccine. Many western countries have switched from oral vaccine to the injected inactivated vaccine to avoid the problem of vaccine- induced paralysis, which could be associated with the oral live attenuated vaccine.

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Replication of echo virus type 25 JV-4 reference strain and wild type strains in MRC5 cells compared with that of poliovirus type 1

Archives of Virology ◽

10.1007/bf01309479 ◽

1994 ◽

Vol 137 (3-4) ◽

pp. 327-340

Author(s):

J. -L. Bailly ◽

M. Chambon ◽

H. Peigue-Lafeuille ◽

F. Charbonn�

Keyword(s):

Virus Type ◽

Reference Strain ◽

Wild Type ◽

Poliovirus Type ◽

Echo Virus ◽

Type Strains

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Freeze-substituted fungal cells of Nectria haematococca: A comparison of the macroconidial walls of the adhesion-competent wild type with an adhesion-reduced mutant

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100160996 ◽

1990 ◽

Vol 48 (3) ◽

pp. 688-689

Author(s):

Thecan Caesar-Ton That ◽

Lynn Epstein

Keyword(s):

Freeze Substitution ◽

Uranyl Acetate ◽

Wild Type ◽

Nectria Haematococca ◽

Fruit Extract ◽

Dialysis Tubing ◽

Tube Emergence ◽

Contrast Microscopy ◽

In The Wild ◽

Freeze Damage

Nectria haematococca mating population I (anamorph, Fusarium solani) macroconidia attach to its host (squash) and non-host surfaces prior to germ tube emergence. The macroconidia become adhesive after a brief period of protein synthesis. Recently, Hickman et al. (1989) isolated N. haematococca adhesion-reduced mutants. Using freeze substitution, we compared the development of the macroconidial wall in the wild type in comparison to one of the mutants, LEI.Macroconidia were harvested at 1C, washed by centrifugation, resuspended in a dilute zucchini fruit extract and incubated from 0 - 5 h. During the incubation period, wild type macroconidia attached to uncoated dialysis tubing. Mutant macroconidia did not attach and were collected on poly-L-lysine coated dialysis tubing just prior to freezing. Conidia on the tubing were frozen in liquid propane at 191 - 193C, substituted in acetone with 2% OsO4 and 0.05% uranyl acetate, washed with acetone, and flat-embedded in Epon-Araldite. Using phase contrast microscopy at 1000X, cells without freeze damage were selected, remounted, sectioned and post-stained sequentially with 1% Ba(MnO4)2 2% uranyl acetate and Reynold’s lead citrate. At least 30 cells/treatment were examined.

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Correlation of virus polypeptide structure with attenuation of poliovirus type 1.

Journal of Virology ◽

10.1128/jvi.23.3.811-815.1977 ◽

1977 ◽

Vol 23 (3) ◽

pp. 811-815 ◽

Cited By ~ 9

Author(s):

J B Milstien ◽

J R Walker ◽

L J Eron

Keyword(s):

Poliovirus Type ◽

Polypeptide Structure

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