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Food and Environmental Virology Dec 2018Within the initiatives for poliomyelitis eradication by WHO, Italy activated an environmental surveillance (ES) in 2005. ES complements clinical Acute Flaccid Paralysis...
Within the initiatives for poliomyelitis eradication by WHO, Italy activated an environmental surveillance (ES) in 2005. ES complements clinical Acute Flaccid Paralysis (AFP) surveillance for possible polio cases, detects poliovirus circulation in environmental sewage, and is used to monitor transmission in communities. In addition to polioviruses, the analyses comprised: (i) the monitoring of the presence of non-polio enteroviruses in sewage samples and (ii) the temporal and geographical distribution of the detected viruses. From 2009 to 2015, 2880 sewage samples were collected from eight cities participating in the surveillance. Overall, 1479 samples resulted positive for enteroviruses. No wild-type polioviruses were found, although four Sabin-like polioviruses were detected. The low degree of mutation found in the genomes of these four isolates suggests that these viruses have had a limited circulation in the population. All non-polio enteroviruses belonged to species B and the most frequent serotype was CV-B5, followed by CV-B4, E-11, E-6, E-7, CV-B3, and CV-B2. Variations in the frequency of different serotypes were also observed in different seasons and/or Italian areas. Environmental surveillance in Italy, as part of the 'WHO global polio eradication program', is a powerful tool to augment the polio surveillance and to investigate the silent circulation or the re-emergence of enteroviruses in the population.
Topics: Cities; Enterovirus; Enterovirus Infections; Environmental Monitoring; Humans; Italy; Limit of Detection; Poliomyelitis; Poliovirus; Sewage
PubMed: 29948963
DOI: 10.1007/s12560-018-9350-8 -
The Enzymes 2016Using poliovirus (PV) and its RNA-dependent RNA polymerase (RdRp) as our primary model system, we have advanced knowledge fundamental to the chemistry and fidelity of... (Review)
Review
Using poliovirus (PV) and its RNA-dependent RNA polymerase (RdRp) as our primary model system, we have advanced knowledge fundamental to the chemistry and fidelity of nucleotide addition by nucleic acid polymerase. Two fidelity checkpoints exist prior to nucleotide addition. The first toggles the enzyme between a nucleotide binding-occluded state and a nucleotide binding-competent state. The second represents an ensemble of conformational states of conserved structural motifs that permits retention of the incoming nucleotide in a state competent for phosphoryl transfer long enough for chemistry to occur. Nucleophilic attack of the alpha-phosphorous atom of the incoming nucleotide produces a pentavalent transition state, collapse of which is facilitated by protonation of the pyrophosphate leaving group by a general acid. All of the relevant conformational states of the enzyme are controlled by a network of interacting residues that permits remote-site residues to control active-site function. The current state of the art for PV RdRp enzymology is such that mechanisms governing fidelity of this enzyme can now be targeted genetically and chemically for development of attenuated viruses and antiviral agents, respectively. Application of the knowledge obtained with the PV RdRp to the development of vaccines and antivirals for emerging RNA viruses represents an important goal for the future.
Topics: Nucleotides; Poliovirus; RNA-Dependent RNA Polymerase
PubMed: 27241934
DOI: 10.1016/bs.enz.2016.02.002 -
PloS One 2021Surveillance and detection of polioviruses (PV) remain crucial to monitoring eradication progress. Intratypic differentiation (ITD) using the real-time RT-PCR kit is key...
Surveillance and detection of polioviruses (PV) remain crucial to monitoring eradication progress. Intratypic differentiation (ITD) using the real-time RT-PCR kit is key to the surveillance workflow, where viruses are screened after cell culture isolation before a subset are verified by sequencing. The ITD kit is a series of real-time RT-PCR assays that screens cytopathic effect (CPE)-positive cell cultures using the standard WHO method for virus isolation. Because ITD screening is a critical procedure in the poliovirus identification workflow, validation of performance of real-time PCR platforms is a core requirement for the detection of poliovirus using the ITD kit. In addition, the continual update and improvement of the ITD assays to simplify interpretation in all platforms is necessary to ensure that all real-time machines are capable of detecting positive real-time signals. Four platforms (ABI7500 real-time systems, Bio-Rad CFX96, Stratagene MX3000P, and the Qiagen Rotor-Gene Q) were validated with the ITD kit and a redesigned poliovirus probe. The poliovirus probe in the real-time RT-PCR pan-poliovirus (PanPV) assay was re-designed with a double-quencher (Zen™) to reduce background fluorescence and potential false negatives. The updated PanPV probe was evaluated with a panel consisting of 184 polioviruses and non-polio enteroviruses. To further validate the updated PanPV probe, the new assay was pilot tested in five Global Polio Laboratory Network (GPLN) laboratories (Madagascar, India, Philippines, Pakistan, and Democratic Republic of Congo). The updated PanPV probe performance was shown to reduce background fluorescence and decrease the number of false positives compared to the standard PanPV probe.
Topics: Feces; Laboratories; Poliovirus; Real-Time Polymerase Chain Reaction; Sewage
PubMed: 34358268
DOI: 10.1371/journal.pone.0255795 -
Viruses Apr 2022Genetic recombination in RNA viruses is an important evolutionary mechanism. It contributes to population diversity, host/tissue adaptation, and compromises vaccine...
Genetic recombination in RNA viruses is an important evolutionary mechanism. It contributes to population diversity, host/tissue adaptation, and compromises vaccine efficacy. Both the molecular mechanism and initial products of recombination are relatively poorly understood. We used an established poliovirus-based in vitro recombination assay to investigate the roles of sequence identity and RNA structure, implicated or inferred from an analysis of circulating recombinant viruses, in the process. In addition, we used next-generation sequencing to investigate the early products of recombination after cellular coinfection with different poliovirus serotypes. In independent studies, we find no evidence for a role for RNA identity or structure in determining recombination junctions location. Instead, genome function and fitness are of greater importance in determining the identity of recombinant progeny. These studies provide further insights into this important evolutionary mechanism and emphasize the critical nature of the selection process on a mixed virus population.
Topics: Antigens, Viral; Enterovirus; Enterovirus Infections; Genome, Viral; Humans; Poliovirus; RNA; Recombination, Genetic
PubMed: 35632658
DOI: 10.3390/v14050916 -
Journal of Clinical Microbiology Jul 2017Oral poliovirus vaccine can mutate to regain neurovirulence. To date, evaluation of these mutations has been performed primarily on culture-enriched isolates by using...
Oral poliovirus vaccine can mutate to regain neurovirulence. To date, evaluation of these mutations has been performed primarily on culture-enriched isolates by using conventional Sanger sequencing. We therefore developed a culture-independent, deep-sequencing method targeting the 5' untranslated region (UTR) and P1 genomic region to characterize vaccine-related poliovirus variants. Error analysis of the deep-sequencing method demonstrated reliable detection of poliovirus mutations at levels of <1%, depending on read depth. Sequencing of viral nucleic acids from the stool of vaccinated, asymptomatic children and their close contacts collected during a prospective cohort study in Veracruz, Mexico, revealed no vaccine-derived polioviruses. This was expected given that the longest duration between sequenced sample collection and the end of the most recent national immunization week was 66 days. However, we identified many low-level variants (<5%) distributed across the 5' UTR and P1 genomic region in all three Sabin serotypes, as well as vaccine-related viruses with multiple canonical mutations associated with phenotypic reversion present at high levels (>90%). These results suggest that monitoring emerging vaccine-related poliovirus variants by deep sequencing may aid in the poliovirus endgame and efforts to ensure global polio eradication.
Topics: Child, Preschool; Feces; Female; Genetic Variation; High-Throughput Nucleotide Sequencing; Humans; Infant; Male; Mexico; Mutation; Poliovirus; Poliovirus Vaccine, Oral; Prospective Studies
PubMed: 28468861
DOI: 10.1128/JCM.00144-17 -
The Journal of Infectious Diseases Nov 2014This article reviews the epidemiology of polio, acute flaccid paralysis (AFP) surveillance, and the implementation of supplemental immunization activities (SIAs) in...
BACKGROUND
This article reviews the epidemiology of polio, acute flaccid paralysis (AFP) surveillance, and the implementation of supplemental immunization activities (SIAs) in Afghanistan from 1997 thru 2013.
METHODS
Published reports and unpublished national data on polio cases, AFP surveillance, and SIAs were analyzed. Recommendations from independent advisory groups and Afghan government informed the conclusions.
RESULTS
From 1997 thru 2013, the annual number of confirmed polio cases fluctuated from a low of 4 in 2004 to a high of 80 in 2011. Wild poliovirus types 2 and 3 were last reported in 1997 and 2010, respectively. Circulating vaccine-derived poliovirus type 2 emerged in 2009. AFP surveillance quality in children aged <15 years improved over time, achieving rates>8 per 100,000 population. Since 2001, at least 6 SIAs have been conducted annually.
CONCLUSIONS
Afghanistan has made progress moving closer to eliminating polio. The program struggles to reach all children because of management and accountability problems in the field, inaccessible populations, and inadequate social mobilization. Consequently, too many children are missed during SIAs. Afghanistan adopted a national emergency action plan in 2012 to address these issues, but national elimination will require consistent and complete implementation of proven strategies.
Topics: Adolescent; Afghanistan; Child; Child, Preschool; Disease Eradication; Epidemiological Monitoring; Female; Humans; Incidence; Infant; Male; Poliomyelitis; Poliovirus; Poliovirus Vaccines; Vaccination
PubMed: 25316832
DOI: 10.1093/infdis/jiu022 -
WHO South-East Asia Journal of Public... Sep 2018The last decade has witnessed an exponential expansion of environmental surveillance (ES) of poliovirus in sewage samples in the World Health Organization (WHO)...
The last decade has witnessed an exponential expansion of environmental surveillance (ES) of poliovirus in sewage samples in the World Health Organization (WHO) South-East Asia Region. This has grown from only three sites in Mumbai, India in 2001 to 56 sites in 2017 in Bangladesh, India, Indonesia, Myanmar, Nepal and Thailand. ES is critical to the region in providing evidence of silent transmission of vaccine-derived poliovirus and Sabin-like poliovirus type 2 - especially since the global "switch" to cease use of oral polio vaccine type 2 - and for monitoring the effectiveness of containment activities. This targeted expansion of ES to supplement surveillance for acute flaccid paralysis (AFP) required quality assurance in ES procedures, improvements in the sensitivity of the laboratory-based surveillance system, and establishment of real-time data analysis for evidence-based programmes. ES in the region has provided documentary evidence for the absence of indigenous wild poliovirus in circulation and no importations via international travellers. Post-switch, while no vaccine-derived poliovirus was detected from AFP cases, ES identified five ambiguous vaccine-derived polioviruses in 2016 and early 2017, with no evidence of circulation. Future challenges include monitoring for vaccine-derived poliovirus strains shed for a prolonged time by immunodeficient individuals, and expanding ES to areas lacking sewage networks. To maintain the polio-free status of the WHO South-East Asia Region and achieve a world free of poliomyelitis, critical evaluation of immunization coverage, continued performance of surveillance for acute flaccid paralysis, and enhanced analysis of sewage samples to detect any breach in containment are essential.
Topics: Adolescent; Asia, Southeastern; Child; Child, Preschool; Disease Eradication; Environmental Monitoring; Humans; Infant; Infant, Newborn; Paralysis; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Oral; Poliovirus Vaccines; Program Evaluation; Sewage; World Health Organization
PubMed: 30136671
DOI: 10.4103/2224-3151.239424 -
Emerging Infectious Diseases Jul 2019The Global Polio Eradication Initiative continues to make progress toward the eradication target. Indigenous wild poliovirus (WPV) type 2 was last detected in 1999, WPV... (Meta-Analysis)
Meta-Analysis
The Global Polio Eradication Initiative continues to make progress toward the eradication target. Indigenous wild poliovirus (WPV) type 2 was last detected in 1999, WPV type 3 was last detected in 2012, and over the past 2 years WPV type 1 has been detected only in parts of 2 countries (Afghanistan and Pakistan). Once the eradication of poliomyelitis is achieved, infectious and potentially infectious poliovirus materials retained in laboratories, vaccine production sites, and other storage facilities will continue to pose a risk for poliovirus reintroduction into communities. The recent breach in containment of WPV type 2 in an inactivated poliovirus vaccine manufacturing site in the Netherlands prompted this review, which summarizes information on facility-associated release of polioviruses into communities reported over >8 decades. Successful polio eradication requires the management of poliovirus containment posteradication to prevent the consequences of the reestablishment of poliovirus transmission.
Topics: Animals; Biohazard Release; Disease Eradication; Global Health; Humans; Laboratories; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Inactivated; Poliovirus Vaccine, Oral
PubMed: 31082331
DOI: 10.3201/eid2507.181703 -
Clinical Infectious Diseases : An... Oct 2018In May 2016, countries using oral polio vaccine for routine immunization switched from trivalent oral poliovirus vaccine (tOPV) to bivalent type 1 and 3 OPV (bOPV). This... (Review)
Review
In May 2016, countries using oral polio vaccine for routine immunization switched from trivalent oral poliovirus vaccine (tOPV) to bivalent type 1 and 3 OPV (bOPV). This was done in order to reduce risks from type 2 vaccine-derived polioviruses (VDPV2) and vaccine-associated paralytic poliomyelitis (VAPP) and to introduce ≥1 dose of inactivated poliovirus vaccine (IPV) to mitigate post-switch loss of type 2 immunity. We conducted a literature review of studies that assessed humoral and intestinal immunogenicity induced by the newly recommended schedules. Differences in seroconversion rates were closely associated with both timing of first IPV administration and number of doses administered. All studies demonstrated high levels of immunity for types 1 and 3 regardless of immunization schedule. When administered late in the primary series, a second dose of IPV closed the humoral immunity gap against polio type 2 associated with a single dose. IPV doses and administration schedules appear to have limited impact on type 2 excretion following challenge.
Topics: Disease Eradication; Global Health; Humans; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Inactivated; Poliovirus Vaccine, Oral; Vaccination
PubMed: 30376081
DOI: 10.1093/cid/ciy633 -
Clinical & Translational Oncology :... Mar 2023Medulloblastoma is the most common pediatric malignant brain tumor, consisting of four molecular subgroups (WNT, SHH, Group 3, Group 4) and 12 subtypes. Expression of...
BACKGROUND
Medulloblastoma is the most common pediatric malignant brain tumor, consisting of four molecular subgroups (WNT, SHH, Group 3, Group 4) and 12 subtypes. Expression of the cell surface poliovirus receptor (PVR), CD155, is necessary for entry of the viral immunotherapeutic agent, PVSRIPO, a polio:rhinovirus chimera. CD155, physiologically expressed in the mononuclear phagocytic system, is widely expressed ectopically in solid tumors. The objective of this study is to elucidate CD155 expression as both a receptor for PVSRIPO and a therapeutic target in medulloblastoma.
METHODS
PVR mRNA expression was determined in several patient cohorts and human medulloblastoma cell lines. Patient samples were also analyzed for CD155 expression using immunohistochemistry and cell lines were analyzed using Western Blots. CD155 was blocked using a monoclonal antibody and cell viability, invasion, and migration were assessed.
RESULTS AND DISCUSSION
PVR mRNA expression was highest in the WNT subgroup and lowest in Group 4. PVR expression in the subgroups of medulloblastoma were similar to other pediatric brain and non-brain tumors. PVR expression was largely not associated with subgroup or subtype. Neither PVR protein expression intensity nor frequency were associated with overall survival. PVR expression was elevated in Group 3 patients with metastases but there was no difference in paired primary and metastatic medulloblastoma. Blocking PVR resulted in dose-dependent cell death, decreased invasion in vitro, and modestly inhibited cell migration.
CONCLUSIONS
CD155 is expressed across medulloblastoma subgroups and subtypes. Blocking CD155 results in cell death and decreased cellular invasion. This study provides rationale for CD155-targeting agents including PVSRIPO and antibody-mediated blockade of CD155.
Topics: Humans; Child; Medulloblastoma; Brain Neoplasms; Poliovirus; Cerebellar Neoplasms; RNA, Messenger
PubMed: 36301489
DOI: 10.1007/s12094-022-02975-9