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Food and Environmental Virology Dec 2017Poliovirus surveillance plays a critical role in achieving and certifying eradication and will play a key role in the polio endgame. Environmental surveillance can... (Review)
Review
Poliovirus surveillance plays a critical role in achieving and certifying eradication and will play a key role in the polio endgame. Environmental surveillance can provide an opportunity to detect circulating polioviruses prior to the observation of any acute flaccid paralysis cases. We completed a systematic review of peer-reviewed publications on environmental surveillance for polio including the search terms "environmental surveillance" or "sewage," and "polio," "poliovirus," or "poliomyelitis," and compared characteristics of the resulting studies. The review included 146 studies representing 101 environmental surveillance activities from 48 countries published between 1975 and 2016. Studies reported taking samples from sewage treatment facilities, surface waters, and various other environmental sources, although they generally did not present sufficient details to thoroughly evaluate the sewage systems and catchment areas. When reported, catchment areas varied from 50 to over 7.3 million people (median of 500,000 for the 25% of activities that reported catchment areas, notably with 60% of the studies not reporting this information and 16% reporting insufficient information to estimate the catchment area population size). While numerous studies reported the ability of environmental surveillance to detect polioviruses in the absence of clinical cases, the review revealed very limited information about the costs and limited information to support quantitative population effectiveness of conducting environmental surveillance. This review motivates future studies to better characterize poliovirus environmental surveillance systems and the potential value of information that they may provide in the polio endgame.
Topics: Environmental Monitoring; Fresh Water; Humans; Poliomyelitis; Poliovirus; Sewage
PubMed: 28687986
DOI: 10.1007/s12560-017-9314-4 -
Vaccine Jun 2021Outbreaks of circulating vaccine-derived polioviruses (cVDPVs) pose a threat to the eventual eradication of all polioviruses. In 2017, an outbreak of cVDPV type 2...
BACKGROUND
Outbreaks of circulating vaccine-derived polioviruses (cVDPVs) pose a threat to the eventual eradication of all polioviruses. In 2017, an outbreak of cVDPV type 2 (cVDPV2) occurred in the midst of a war in Syria. We describe vaccination-based risk factors for and the successful response to the outbreak.
METHODS
We performed a descriptive analysis of cVDPV2 cases and key indicators of poliovirus surveillance and vaccination activities during 2016-2018. In the absence of reliable subnational coverage data, we used the caregiver-reported vaccination status of children with non-polio acute flaccid paralysis (AFP) as a proxy for vaccination coverage. We then estimated the relative odds of being unvaccinated against polio, comparing children in areas affected by the outbreak to children in other parts of Syria in order to establish the presence of poliovirus immunity gaps in outbreak affected areas.
FINDINGS
A total of 74 cVDPV2 cases were reported, with paralysis onset ranging from 3 March to 21 September 2017. All but three cases were reported from Deir-ez-Zor governorate and 84% had received < 3 doses of oral poliovirus vaccine (OPV). After adjusting for age and sex, non-polio AFP case-patients aged 6-59 months in outbreak-affected areas had 2.5 (95% CI: 1.1-5.7) increased odds of being unvaccinated with OPV compared with non-polio AFP case-patients in the same age group in other parts of Syria. Three outbreak response rounds of monovalent OPV type 2 (mOPV2) vaccination were conducted, with governorate-level coverage mostly exceeding 80%.
INTERPRETATION
Significant declines in both national and subnational polio vaccination coverage, precipitated by war and a humanitarian crisis, led to a cVDPV2 outbreak in Syria that was successfully contained following three rounds of mOPV2 vaccination.
Topics: Child; Disease Outbreaks; Humans; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Oral; Syria
PubMed: 34053791
DOI: 10.1016/j.vaccine.2021.05.045 -
MBio Feb 2021Genome transfer from a virus into a cell is a critical early step in viral replication. Enveloped viruses achieve the delivery of their genomes into the cytoplasm by...
Genome transfer from a virus into a cell is a critical early step in viral replication. Enveloped viruses achieve the delivery of their genomes into the cytoplasm by merging the viral membrane with the cellular membrane via a conceptually simple mechanism called membrane fusion. In contrast, genome translocation mechanisms in nonenveloped viruses, which lack viral membranes, remain poorly understood. Although cellular assays provide useful information about cell entry and genome release, it is difficult to obtain detailed mechanistic insights due both to the inherent technical difficulties associated with direct visualization of these processes and to the prevalence of nonproductive events in cellular assays performed at a very high multiplicity of infection. To overcome these issues, we developed an single-particle fluorescence assay to characterize genome release from a nonenveloped virus (poliovirus) in real time using a tethered receptor-decorated liposome system. Our results suggest that poliovirus genome release is a complex process that consists of multiple rate-limiting steps. Interestingly, we found that the addition of exogenous wild-type capsid protein VP4, but not mutant VP4, enhanced the efficiency of genome translocation. These results, together with prior structural analysis, suggest that VP4 interacts with RNA directly and forms a protective, membrane-spanning channel during genome translocation. Furthermore, our data indicate that VP4 dynamically interacts with RNA, rather than forming a static tube for RNA translocation. This study provides new insights into poliovirus genome translocation and offers a cell-free assay that can be utilized broadly to investigate genome release processes in other nonenveloped viruses. The initial transfer of genomic material from a virus into a host cell is a key step in any viral infection. Consequently, understanding how viruses deliver their genomes into cells could reveal attractive therapeutic targets. Although conventional biochemical and cellular assays have provided useful information about cell entry, the mechanism used to deliver the viral genomes across the cellular membrane into the cytoplasm is not well characterized for nonenveloped viruses such as poliovirus. In this study, we developed a fluorescence imaging assay to visualize poliovirus genome release using a synthetic vesicle system. Our results not only provide new mechanistic insights into poliovirus genome translocation but also offer a cell-free assay to bridge gaps in understanding of this process in other nonenveloped viruses.
Topics: Capsid Proteins; Computer Systems; Genome, Viral; HeLa Cells; Host Microbial Interactions; Humans; In Vitro Techniques; Liposomes; Optical Imaging; Poliovirus; RNA, Viral; Virus Internalization
PubMed: 33622727
DOI: 10.1128/mBio.03695-20 -
Current Opinion in Virology Oct 2020Dendritic cells (DCs) are pivotal stimulators of T cell responses. They provide essential signals (epitope presentation, proinflammatory cytokines, co-stimulation) to T... (Review)
Review
Dendritic cells (DCs) are pivotal stimulators of T cell responses. They provide essential signals (epitope presentation, proinflammatory cytokines, co-stimulation) to T cells and prime adaptive immunity. Therefore, they are paramount to immunization strategies geared to generate T cell immunity. The inflammatory signals DCs respond to, classically occur in the context of acute virus infection. Yet, enlisting viruses for engaging DCs is hampered by their penchant for targeting DCs with sophisticated immune evasive and suppressive ploys. In this review, we discuss our work on devising vectors based on a recombinant polio:rhinovirus chimera for effectively targeting and engaging DCs. We are juxtaposing this approach with commonly used, recently studied dsDNA virus vector platforms.
Topics: Adaptive Immunity; Animals; Antigen Presentation; Dendritic Cells; Genetic Vectors; Humans; Immune Evasion; Immunity, Innate; Mice; Poliovirus; T-Lymphocytes; Viral Tropism; Viral Vaccines
PubMed: 32771959
DOI: 10.1016/j.coviro.2020.07.012 -
Journal of Virological Methods Feb 2022The cross-contamination of cell lines in culture is a persistent problem. Genetically modified L20B (Mouse) and RD (Human Rhabdomyosarcoma) cell lines are commonly used...
Development and Evaluation of a TaqMan Real-Time PCR Assay for the Rapid Detection of Cross-Contamination of RD (Human) and L20B (Mouse) Cell Lines Used in Poliovirus Surveillance.
BACKGROUND
The cross-contamination of cell lines in culture is a persistent problem. Genetically modified L20B (Mouse) and RD (Human Rhabdomyosarcoma) cell lines are commonly used in poliovirus research, surveillance, and diagnostics. Cross-contamination between these cell lines leads to unreproducible results and unreliable surveillance data, negatively affecting public health. The gold standard method for cell authentication is Short Tandem Repeats analysis, which is time-consuming and expensive. The disadvantage of STR is limited detection of interspecies contamination.
METHODS
This assay targets the mitochondrial cytochrome c oxidase subunit I (MTCO1) gene, a highly conserved and emergent DNA barcode region for detection of cross-contamination in RD and L20B cell lines. The MagNA Pure Compact instrument and ABI 7500 Fast Dx Real-time PCR systems were used for DNA extraction and to perform real-time PCR respectively.
RESULTS
The newly developed assay is very sensitive with a limit of detection of 100 RD cells/1 million L20B/mL. The amplification efficiency and R-value were 102.26% and 0.9969 respectively. We evaluated specificity of the assay with five human and four mouse cell lines, as well as monkey and rat cell lines. The assay showed no cross-reactivity with genomic DNA from human, mouse, rat, or monkey cell lines. The analytical sensitivity was also evaluated by spiking varying amounts of RD cells (0.001% - 10%) into L20B cells. There was no difference in C values when running single-plex or duplex PCR reactions with similar experimental conditions.
CONCLUSIONS
We have developed and validated a TaqMan real-time PCR assay, a sensitive method for the detection of cross-contamination of RD and L20B cell lines.
Topics: Animals; Cell Line; Haplorhini; Humans; Mice; Nucleic Acid Amplification Techniques; Poliovirus; Rats; Real-Time Polymerase Chain Reaction; Sensitivity and Specificity
PubMed: 34774617
DOI: 10.1016/j.jviromet.2021.114354 -
International Health Mar 2023
Topics: Humans; Poliovirus; Poliomyelitis; Poliovirus Vaccine, Oral; Global Health; Disease Eradication
PubMed: 36271900
DOI: 10.1093/inthealth/ihac068 -
MMWR. Morbidity and Mortality Weekly... Apr 2019When the Global Polio Eradication Initiative (GPEI) began in 1988, cases of poliomyelitis were reported from 125 countries. Since then, only Afghanistan, Nigeria, and...
When the Global Polio Eradication Initiative (GPEI) began in 1988, cases of poliomyelitis were reported from 125 countries. Since then, only Afghanistan, Nigeria, and Pakistan have experienced uninterrupted transmission of wild poliovirus (WPV). The primary means of detecting poliovirus is through surveillance for acute flaccid paralysis (AFP) among children aged <15 years with testing of stool specimens for WPV and vaccine-derived polioviruses (VDPVs) in World Health Organization (WHO)-accredited laboratories of the Global Polio Laboratory Network (GPLN) (1,2). AFP surveillance is supplemented by environmental surveillance for polioviruses in sewage at selected locations. Analysis of genomic sequences of isolated polioviruses enables assessment of transmission by time and place, potential gaps in surveillance, and emergence of VDPVs (3). This report presents 2017-2018 poliovirus surveillance data, focusing on 31 countries* identified as high-priority countries because of a "high risk of poliovirus transmission and limited capacity to adequately address those risks" (4). Some of these countries are located within WHO regions with endemic polio, and others are in regions that are polio-free. In 2018, 26 (84%) of the 31 countries met AFP surveillance indicators nationally; however, subnational variation in surveillance performance was substantial. Surveillance systems need continued strengthening through monitoring, supervision, and improvements in specimen collection and transport to provide sufficient evidence for interruption of poliovirus circulation.
Topics: Acute Disease; Adolescent; Child; Child, Preschool; Disease Eradication; Environmental Monitoring; Feces; Global Health; Humans; Infant; Laboratories; Paralysis; Poliomyelitis; Poliovirus; Population Surveillance
PubMed: 30946737
DOI: 10.15585/mmwr.mm6813a4 -
Vaccine Mar 2015Vaccine-derived polioviruses (VDPVs), strains of poliovirus mutated from the oral polio vaccine, pose a challenge to global polio eradication. Immunodeficiency-related... (Review)
Review
BACKGROUND
Vaccine-derived polioviruses (VDPVs), strains of poliovirus mutated from the oral polio vaccine, pose a challenge to global polio eradication. Immunodeficiency-related vaccine-derived polioviruses (iVDPVs) are a type of VDPV which may serve as sources of poliovirus reintroduction after the eradication of wild-type poliovirus. This review is a comprehensive update of confirmed iVDPV cases published in the scientific literature from 1962 to 2012, and describes clinically relevant trends in reported iVDPV cases worldwide.
METHODS
We conducted a systematic review of published iVDPV case reports from January 1960 to November 2012 from four databases. We included cases in which the patient had a primary immunodeficiency, and the vaccine virus isolated from the patient either met the sequencing definition of VDPV (>1% divergence for serotypes 1 and 3 and >0.6% for serotype 2) and/or was previously reported as an iVDPV by the World Health Organization.
RESULTS
We identified 68 iVDPV cases in 49 manuscripts reported from 25 countries and the Palestinian territories. 62% of case patients were male, 78% presented clinically with acute flaccid paralysis, and 65% were iVDPV2. 57% of cases occurred in patients with predominantly antibody immunodeficiencies, and the overall all-cause mortality rate was greater than 60%. The median age at case detection was 1.4 years [IQR: 0.8, 4.5] and the median duration of shedding was 1.3 years [IQR: 0.7, 2.2]. We identified a poliovirus genome VP1 region mutation rate of 0.72% per year and a higher median percent divergence for iVDPV1 cases. More cases were reported from high income countries, which also had a larger age variation and different distribution of immunodeficiencies compared to upper and lower middle-income countries.
CONCLUSION
Our study describes the incidence and characteristics of global iVDPV cases reported in the literature in the past five decades. It also highlights the regional and economic disparities of reported iVDPV cases.
Topics: Capsid Proteins; Disease Eradication; Female; Humans; Immunologic Deficiency Syndromes; Male; Mutation Rate; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Oral; Vaccination
PubMed: 25600519
DOI: 10.1016/j.vaccine.2015.01.018 -
Vaccine Apr 2023The Global Polio Eradication Initiative introduced novel oral polio vaccine Type 2 (nOPV2) to address circulating vaccine-derived poliovirus Type 2 (cVDPV2). Although...
BACKGROUND
The Global Polio Eradication Initiative introduced novel oral polio vaccine Type 2 (nOPV2) to address circulating vaccine-derived poliovirus Type 2 (cVDPV2). Although nOPV2 is a more genetically stable vaccine, it may not have the immediate trust of communities and health workers due to its novelty, potential side effects, and introduction under an Emergency Use Listing (EUL). We explored how nOPV2 introduction might be perceived by stakeholders and identified communications barriers related to nOPV2 hesitancy.
METHODS
This work was conducted in the Democratic Republic of the Congo, Kenya, and Nigeria between January and March 2020. We used a rapid qualitative approach to conduct focus group discussions and in-depth interviews with four stakeholder groups: caregivers of children under 5, polio frontline workers, healthcare practitioners, and social/health influencers. Data are presented according to awareness, attitudes/beliefs, and concerns about cVDPV2 and nOPV2.
RESULTS
Stakeholders were largely unaware of cVDPV2. The causes of recent polio outbreaks were characterized as poor sanitation, under-immunization/in-migration, or poor vaccine management procedures. Caregivers were aware of and concerned by repeated vaccination campaigns. All stakeholder groups anticipated initial hesitancy, fear, and suspicion from caregivers due to nOPV2 introduction, with primary concerns linked to vaccine testing, safety, effectiveness, side effects, and support from authorities. Stakeholders thought the term "genetic modification" could be controversial but that introduction under an EUL would be acceptable given the emergency nature of cVDPV2 outbreaks. Stakeholders called for adequate and timely information to counter concerns.
CONCLUSIONS
Despite initial concerns, stakeholders felt nOPV2 would ultimately be accepted by caregivers. However, public health officials have a small window for "getting things right" when introducing nOPV2. Strategic communication interventions addressing key concerns and targeted communications with stakeholder groups, especially frontline workers, could improve community acceptance of nOPV2.
Topics: Child; Humans; Poliovirus; Nigeria; Kenya; Democratic Republic of the Congo; Public Opinion; Poliovirus Vaccine, Oral; Poliomyelitis; Disease Outbreaks
PubMed: 35871107
DOI: 10.1016/j.vaccine.2022.05.020 -
MBio Dec 2015Viruses of the Enterovirus genus of picornaviruses, including poliovirus, coxsackievirus B3 (CVB3), and human rhinovirus, commandeer the functions of host cell proteins...
UNLABELLED
Viruses of the Enterovirus genus of picornaviruses, including poliovirus, coxsackievirus B3 (CVB3), and human rhinovirus, commandeer the functions of host cell proteins to aid in the replication of their small viral genomic RNAs during infection. One of these host proteins is a cellular DNA repair enzyme known as 5' tyrosyl-DNA phosphodiesterase 2 (TDP2). TDP2 was previously demonstrated to mediate the cleavage of a unique covalent linkage between a viral protein (VPg) and the 5' end of picornavirus RNAs. Although VPg is absent from actively translating poliovirus mRNAs, the removal of VPg is not required for the in vitro translation and replication of the RNA. However, TDP2 appears to be excluded from replication and encapsidation sites during peak times of poliovirus infection of HeLa cells, suggesting a role for TDP2 during the viral replication cycle. Using a mouse embryonic fibroblast cell line lacking TDP2, we found that TDP2 is differentially required among enteroviruses. Our single-cycle viral growth analysis shows that CVB3 replication has a greater dependency on TDP2 than does poliovirus or human rhinovirus replication. During infection, CVB3 protein accumulation is undetectable (by Western blot analysis) in the absence of TDP2, whereas poliovirus protein accumulation is reduced but still detectable. Using an infectious CVB3 RNA with a reporter, CVB3 RNA could still be replicated in the absence of TDP2 following transfection, albeit at reduced levels. Overall, these results indicate that TDP2 potentiates viral replication during enterovirus infections of cultured cells, making TDP2 a potential target for antiviral development for picornavirus infections.
IMPORTANCE
Picornaviruses are one of the most prevalent groups of viruses that infect humans and livestock worldwide. These viruses include the human pathogens belonging to the Enterovirus genus, such as poliovirus, coxsackievirus B3 (CVB3), and human rhinovirus. Diseases caused by enteroviruses pose a major problem for public health and have significant economic impact. Poliovirus can cause paralytic poliomyelitis. CVB3 can cause hand, foot, and mouth disease and myocarditis. Human rhinovirus is the causative agent of the common cold, which has a severe economic impact due to lost productivity and severe health consequences in individuals with respiratory dysfunction, such as asthma. By gaining a better understanding of the enterovirus replication cycle, antiviral drugs against enteroviruses may be developed. Here, we report that the absence of the cellular enzyme TDP2 can significantly decrease viral yields of poliovirus, CVB3, and human rhinovirus, making TDP2 a potential target for an antiviral against enterovirus infections.
Topics: Animals; DNA Repair Enzymes; DNA-Binding Proteins; Enterovirus; Enterovirus B, Human; Enterovirus Infections; HeLa Cells; Host-Pathogen Interactions; Humans; Mice; Phosphoric Diester Hydrolases; Poliovirus; RNA, Viral; Rhinovirus; Tumor Necrosis Factor Receptor-Associated Peptides and Proteins; Viral Proteins; Virus Replication
PubMed: 26715620
DOI: 10.1128/mBio.01931-15