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Tanpakushitsu Kakusan Koso. Protein,... Oct 1992
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Water Science and Technology : a... 2008The last case of polio in Cyprus caused by a wild-type poliovirus occurred in 1995. Since then Cyprus belongs to the countries considered poliovirus-free by the WHO. The...
The last case of polio in Cyprus caused by a wild-type poliovirus occurred in 1995. Since then Cyprus belongs to the countries considered poliovirus-free by the WHO. The aim of this study was to confirm the absence of any circulating wild-type polioviruses and to monitor vaccine-derived polioviruses in Cyprus by analysis of sewages. During the course of this study no wild-type polioviruses were identified, although the identification of viable oral poliovirus vaccine isolates confirmed the presence and circulation of poliovirus vaccine strains in sewage in Cyprus.
Topics: Cyprus; Environmental Monitoring; Humans; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Oral; Reverse Transcriptase Polymerase Chain Reaction; Sewage
PubMed: 18725734
DOI: 10.2166/wst.2008.425 -
Journal of Medicinal Chemistry Jan 2019The final stages of polio eradication are proving more difficult than the early phases, and the development of effective drugs and treatments is considered a priority;...
The final stages of polio eradication are proving more difficult than the early phases, and the development of effective drugs and treatments is considered a priority; thus, the research is ongoing. A screening of our in-house chemical library against poliovirus Sabin strains led to the identification of compounds 5 and 6 as hits active at submicromolar concentrations. Derivatives of these compounds were synthesized as a preliminary structure-activity-relationship study. Among them, 7 and 11 were highly active against poliovirus Sabin 1-3. Compound 11 was also very potent against a large panel of wild and vaccine-derived polioviruses. Time-of-addition experiments suggest that 5 and 7 could be active at an early stage of viral replication, whereas 11 was active at same concentration at all stages of viral replication. A ligand-based approach was applied to find the common structural features shared by the new compounds and already-known poliovirus inhibitors.
Topics: Antiviral Agents; Binding Sites; HeLa Cells; Humans; Molecular Dynamics Simulation; Oxazoles; Poliovirus; Structure-Activity Relationship; Virus Replication
PubMed: 30512950
DOI: 10.1021/acs.jmedchem.8b01482 -
Reviews of Infectious Diseases 1984During 1952-1954, some of the first papers were published on the attenuation of wild poliovirus for vaccine purposes. These efforts soon came to fruition , and...
During 1952-1954, some of the first papers were published on the attenuation of wild poliovirus for vaccine purposes. These efforts soon came to fruition , and large-scale field trials were held in many countries under a variety of conditions. Routine use of live oral poliovirus vaccines ( OPV ) was begun in many countries during the spring of 1960, and vaccines made from the Sabin strains were licensed in the United States in 1961-1962. In the early years of immunization with OPV , vaccines were usually monovalent, but a trivalent vaccine is now used. Throughout the world the introduction and continued proper use of OPV has been followed by a striking decrease in the number of paralytic cases. This dramatic and persistent outcome has stimulated recent discussions on the possible eradication of the disease. This paper reviews the criteria for the selection of vaccine strains that now make up the OPV , thermal stabilization of OPV , safety precautions that are followed in the manufacture of OPV , genetic stability of OPV strains following replication in vaccines and their contacts, and potential incorporation into OPV of totally attenuated polioviruses that can no longer revert to neurovirulence because the regions of the viral genome associated with neurovirulence are deleted or altered.
Topics: Animals; Genes, Viral; Hot Temperature; Humans; Poliovirus; Poliovirus Vaccine, Oral; Vaccines, Attenuated; World Health Organization
PubMed: 6330836
DOI: 10.1093/clinids/6.supplement_2.s323 -
Acta Virologica Apr 2000The oral poliovirus vaccine (OPV) has been effectively used in the control of poliomyelitis and in the eradication of wild polioviruses. Although there are many... (Review)
Review
The oral poliovirus vaccine (OPV) has been effectively used in the control of poliomyelitis and in the eradication of wild polioviruses. Although there are many advantages in using attenuated OPV strains in the campaign to eradicate poliomyelitis, several studies have demonstrated that there are some disadvantages such as (a) excretion by vaccines of OPV-derived polioviruses with genomic modifications known to increase the neurovirulence, (b) appearance of vaccine-associated paralytic poliomyelitis (VAPP) and other adverse effects in vaccinees, (c) occurrence of persistent infections caused by OPV-derived strains in immunodeficient patients with VAPP, (d) transmission of OPV-derived polioviruses to susceptible individuals which develop VAPP, and (e) detection of OPV-derived polioviruses in the environment, which could be a source of infection for humans in the future. Different studies indicate that it is important to consider the possibility of persistent infections and excretion of OPV-derived polioviruses for long periods by humans, and also the survival in the environment of OPV-derived polioviruses excreted by humans, which could be transmitted and circulate in a non-immune population after stopping poliovirus vaccination. The findings reported here may have important implications for global poliomyelitis eradication initiative and indicate that surveillance of OPV-derived strains will also be important in the final step of eradication of poliomyelitis from the planet.
Topics: Animals; Environment; Evolution, Molecular; Genome, Viral; Global Health; Humans; Nervous System Diseases; Paralysis; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Oral; Virus Replication
PubMed: 10989702
DOI: No ID Found -
Cell Host & Microbe Jan 2021The emergence of circulating vaccine-derived polioviruses through evolution of the oral polio vaccine (OPV) poses a significant obstacle to polio eradication....
The emergence of circulating vaccine-derived polioviruses through evolution of the oral polio vaccine (OPV) poses a significant obstacle to polio eradication. Understanding the early genetic changes that occur as OPV evolves and transmits is important for preventing future outbreaks. Here, we use deep sequencing to define the evolutionary trajectories of type 2 OPV in a vaccine trial. By sequencing 497 longitudinal stool samples from 271 OPV2 recipients and household contacts, we were able to examine the extent of convergent evolution in vaccinated individuals and the amount of viral diversity that is transmitted. In addition to rapid reversion of key attenuating mutations, we identify strong selection at 19 sites across the genome. We find that a tight transmission bottleneck limits the onward transmission of these early adaptive mutations. Our results highlight the distinct evolutionary dynamics of live attenuated virus vaccines and have important implications for the success of next-generation OPV.
Topics: Evolution, Molecular; Feces; Genetic Variation; Genome, Viral; High-Throughput Nucleotide Sequencing; Humans; Mutation; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Oral; Randomized Controlled Trials as Topic; Selection, Genetic; Vaccines, Attenuated; Whole Genome Sequencing
PubMed: 33212020
DOI: 10.1016/j.chom.2020.10.011 -
PLoS Pathogens Jun 2008RNA viruses such as poliovirus have high mutation rates, and a diverse viral population is likely required for full virulence. We previously identified limitations on...
RNA viruses such as poliovirus have high mutation rates, and a diverse viral population is likely required for full virulence. We previously identified limitations on poliovirus spread after peripheral injection of mice expressing the human poliovirus receptor (PVR), and we hypothesized that the host interferon response may contribute to the viral bottlenecks. Here, we examined poliovirus population bottlenecks in PVR mice and in PVR mice that lack the interferon alpha/beta receptor (PVR-IFNAR-/-), an important component of innate immunity. To monitor population dynamics, we developed a pool of ten marked polioviruses discriminated by a novel hybridization-based assay. Following intramuscular or intraperitoneal injection of the ten-virus pool, a major bottleneck was observed during transit to the brain in PVR mice, but was absent in PVR-IFNAR-/- mice, suggesting that the interferon response was a determinant of the peripheral site-to-brain bottleneck. Since poliovirus infects humans by the fecal-oral route, we tested whether bottlenecks exist after oral inoculation of PVR-IFNAR-/- mice. Despite the lack of a bottleneck following peripheral injection of PVR-IFNAR-/- mice, we identified major bottlenecks in orally inoculated animals, suggesting physical barriers may contribute to the oral bottlenecks. Interestingly, two of the three major bottlenecks we identified were partially overcome by pre-treating mice with dextran sulfate sodium, which damages the colonic epithelium. Overall, we found that viral trafficking from the gut to other body sites, including the CNS, is a very dynamic, stochastic process. We propose that multiple host barriers and the resulting limited poliovirus population diversity may help explain the rare occurrence of viral CNS invasion and paralytic poliomyelitis. These natural host barriers are likely to play a role in limiting the spread of many microbes.
Topics: Animals; Biological Transport; Central Nervous System; Feces; Gastrointestinal Tract; Genetic Variation; Humans; Immunity; Mice; Molecular Sequence Data; Poliovirus; Receptor, Interferon alpha-beta; Receptors, Virus; Virulence; Virus Replication
PubMed: 18535656
DOI: 10.1371/journal.ppat.1000082 -
Acta Virologica Jun 1998The oral poliovirus vaccine (OPV) has been effectively used in the reduction and control of poliomyelitis cases on the planet. Despite several advantages of using the... (Review)
Review
The oral poliovirus vaccine (OPV) has been effectively used in the reduction and control of poliomyelitis cases on the planet. Despite several advantages of using the attenuated OPV strains, the rare occurrence of vaccine-associated paralytic poliomyelitis (VAPP) cases in vaccine recipients and their susceptible contacts is a disadvantage. Molecular biology studies of polioviruses isolated from stool and central nervous system (CNS) of patients with VAPP have confirmed the vaccine origin of the isolates and demonstrated genomic modifications known or suspected to increase the neurovirulence. Similar genomic modifications have also been identified in OPV-derived strains isolated from healthy vaccinees and healthy contacts, suggesting that host factors are also involved in the establishment of poliomyelitis. Other neurologic complications such as meningitis, encephalitis, convulsions, transverse myelitis and Guillain-Barré syndrome have also been rarely associated with the use of this vaccine. The characterization of polioviruses isolated from such cases has demonstrated their OPV origin.
Topics: Feces; Genome, Viral; Humans; Mutation; Nervous System; Nervous System Diseases; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Oral; Recombination, Genetic
PubMed: 9842449
DOI: No ID Found -
Journal of Medical Virology Jul 2014The study describes genetic characterization of poliovirus (PV) strains isolated from sewage samples in Poland. The analyses were performed for the detection of any...
The study describes genetic characterization of poliovirus (PV) strains isolated from sewage samples in Poland. The analyses were performed for the detection of any putative polio revertants and recombinants in three genomic regions by sequencing analysis. Thirty-six strains were analyzed. The analyzed strains were identified by neutralization assay as 7 strains of serotype P1, 10 strains of serotype P2, and 19 strains of serotype P3. Sewage isolates were sequenced in 5'UTR, VP1, and 3D genomic regions. All detected PVs were classified as vaccine strains on the basis of VP1 sequence. Mutational differences in the VP1 sequences of isolated viruses ranged from 0.0% to 0.4%, indicating a limited replication period. The genetic analysis of the 3D region showed that some strains have recombinant genomes. Nine strains were found as dipartite recombinants (seven strains--S3/S2, one strain--S2/S1, one strain--S3/S1), while one strain was found as tripartite recombinant (S3/S2/S1). No recombinants with non-PV enteroviruses were identified. None of wild-type PVs or vaccine-derived polioviruses (VDPVs) were detected. This study showed the absence of wild or VDPV circulation in the country and demonstrated the usefulness of environmental surveillance in addition to acute flaccid paralysis (AFP) surveillance in support of polio eradication initiatives.
Topics: 5' Untranslated Regions; Capsid Proteins; Humans; Mutation; Neutralization Tests; Poland; Poliovirus; RNA, Viral; RNA-Dependent RNA Polymerase; Recombination, Genetic; Sequence Analysis, DNA; Serotyping; Sewage
PubMed: 24123142
DOI: 10.1002/jmv.23803 -
Transfusion Dec 2018Wild-type poliovirus may be eradicated soon and under WHO GAPIII guidance, laboratory use will be discontinued or subject to strict containment. Per US Code of Federal...
BACKGROUND
Wild-type poliovirus may be eradicated soon and under WHO GAPIII guidance, laboratory use will be discontinued or subject to strict containment. Per US Code of Federal Regulations, however, immunoglobulin lot release testing will still require use of replicating poliovirus. The suitability of S19 hyper-attenuated and apathogenic poliovirus strains as alternatives to the currently used wild-type virus in such a release assay was investigated.
STUDY DESIGN AND METHODS
S19 poliovirus strains were propagated in a commercial setting using good virological practices and maintenance of the S19 hyper-attenuated genotype was confirmed by massively parallel sequencing.
RESULTS
The attenuated phenotype of the produced S19 stocks was confirmed in a highly sensitive mouse-model. Equivalency in performance was seen in the lot release assay for the S19 and wild-type polioviruses.
CONCLUSION
The deployment of such hyper-attenuated and thoroughly characterized S19 stocks in these and other essential activities might reconcile final containment measures with continued safe use of poliovirus.
Topics: Animals; Disease Eradication; Female; Genetic Variation; Humans; Immunoglobulins; Male; Mice; Mice, Transgenic; Poliomyelitis; Poliovirus; Vaccines, Attenuated; Virology
PubMed: 30536436
DOI: 10.1111/trf.15048