-
Current Opinion in Virology Aug 2015An oncolytic virus (OV) based on poliovirus (PV), the highly attenuated polio/rhinovirus recombinant PVSRIPO, may deliver targeted inflammatory cancer cell killing; a... (Review)
Review
An oncolytic virus (OV) based on poliovirus (PV), the highly attenuated polio/rhinovirus recombinant PVSRIPO, may deliver targeted inflammatory cancer cell killing; a principle that is showing promise in clinical trials for recurrent glioblastoma (GBM). The two decisive factors in PVSRIPO anti-tumor efficacy are selective cytotoxicity and its in situ immunogenic imprint. While our work is focused on what constitutes PVSRIPO cancer cytotoxicity, we are also studying how this engenders host immune responses that are vital to tumor regression. We hypothesize that PVSRIPO cytotoxicity and immunogenicity are inextricably linked in essential, complimentary roles that define the anti-neoplastic response. Herein we delineate mechanisms we unraveled to decipher the basis for PVSRIPO cytotoxicity and its immunotherapeutic potential.
Topics: Animals; Glioblastoma; Humans; Oncolytic Virotherapy; Oncolytic Viruses; Poliovirus
PubMed: 26083317
DOI: 10.1016/j.coviro.2015.05.007 -
Virology May 2015How do viruses spread from cell to cell? Enveloped viruses acquire their surrounding membranes by budding. If a newly enveloped virus has budded through the plasma... (Review)
Review
How do viruses spread from cell to cell? Enveloped viruses acquire their surrounding membranes by budding. If a newly enveloped virus has budded through the plasma membrane, it finds itself outside the cell immediately. If it has budded through the bounding membrane of an internal compartment such as the ER, the virus finds itself in the lumen, from which it can exit the cell via the conventional secretion pathway. Thus, although some enveloped viruses destroy the cells they infect, there is no topological need to do so. On the other hand, naked viruses such as poliovirus lack an external membrane. They are protein-nucleic acid complexes within the cytoplasm or nucleus of the infected cell, like a ribosome, a spliceosome or an aggregate of Huntingtin protein. The simplest way for such a particle to pass through the single lipid bilayer that separates it from the outside of the cell would be to violate the integrity of that bilayer. Thus, it is not surprising that the primary mode of exit for non-enveloped viruses is cell lysis. However, more complex exit strategies are possible, such as the creation of new compartments whose complex topologies allow the exit of cytoplasm and its contents without violating the integrity of the cell. Here we will discuss the non-lytic spread of poliovirus and recent observations of such compartments during viral infection with several different picornaviruses.
Topics: Humans; Poliovirus; Virus Release
PubMed: 25890822
DOI: 10.1016/j.virol.2015.03.044 -
Vaccine Jun 2023Prior modeling studies showed that current outbreak management strategies are unlikely to stop outbreaks caused by type 1 wild polioviruses (WPV1) or circulating...
Prior modeling studies showed that current outbreak management strategies are unlikely to stop outbreaks caused by type 1 wild polioviruses (WPV1) or circulating vaccine-derived polioviruses (cVDPVs) in many areas, and suggested increased risks of outbreaks with cocirculation of more than one type of poliovirus. The surge of type 2 poliovirus transmission that began in 2019 and continues to date, in conjunction with decreases in preventive supplemental immunization activities (SIAs) for poliovirus types 1 and 3, has led to the emergence of several countries with cocirculation of more than one type of poliovirus. Response to these emerging cocirculation events is theoretically straightforward, but the different formulations, types, and inventories of oral poliovirus vaccines (OPVs) available for outbreak response present challenging practical questions. In order to demonstrate the implications of using different vaccine options and outbreak campaign strategies, we applied a transmission model to a hypothetical population with conditions similar to populations currently experiencing outbreaks of cVDPVs of both types 1 and 2. Our results suggest prevention of the largest number of paralytic cases occurs when using (1) trivalent OPV (tOPV) (or coadministering OPV formulations for all three types) until one poliovirus outbreak type dies out, followed by (2) using a type-specific OPV until the remaining poliovirus outbreak type also dies out. Using tOPV first offers a lower overall expected cost, but this option may be limited by the willingness to expose populations to type 2 Sabin OPV strains. For strategies that use type 2 novel OPV (nOPV2) concurrently administered with bivalent OPV (bOPV, containing types 1 and 3 OPV) emerges as a leading option, but questions remain about feasibility, logistics, type-specific take rates, and coadministration costs.
Topics: Humans; Disease Outbreaks; Global Health; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Inactivated; Poliovirus Vaccine, Oral
PubMed: 37121801
DOI: 10.1016/j.vaccine.2023.04.037 -
PLoS Pathogens Sep 2021During replication, RNA viruses accumulate genome alterations, such as mutations and deletions. The interactions between individual variants can determine the fitness of...
During replication, RNA viruses accumulate genome alterations, such as mutations and deletions. The interactions between individual variants can determine the fitness of the virus population and, thus, the outcome of infection. To investigate the effects of defective interfering genomes (DI) on wild-type (WT) poliovirus replication, we developed an ordinary differential equation model, which enables exploring the parameter space of the WT and DI competition. We also experimentally examined virus and DI replication kinetics during co-infection, and used these data to infer model parameters. Our model identifies, and our experimental measurements confirm, that the efficiencies of DI genome replication and encapsidation are two most critical parameters determining the outcome of WT replication. However, an equilibrium can be established which enables WT to replicate, albeit to reduced levels.
Topics: Coinfection; Defective Viruses; Humans; Models, Theoretical; Poliovirus; Virus Replication
PubMed: 34570820
DOI: 10.1371/journal.ppat.1009277 -
The Journal of Infectious Diseases Nov 2014This article summarizes the status of environmental surveillance (ES) used by the Global Polio Eradication Initiative, provides the rationale for ES, gives examples of... (Review)
Review
This article summarizes the status of environmental surveillance (ES) used by the Global Polio Eradication Initiative, provides the rationale for ES, gives examples of ES methods and findings, and summarizes how these data are used to achieve poliovirus eradication. ES complements clinical acute flaccid paralysis (AFP) surveillance for possible polio cases. ES detects poliovirus circulation in environmental sewage and is used to monitor transmission in communities. If detected, the genetic sequences of polioviruses isolated from ES are compared with those of isolates from clinical cases to evaluate the relationships among viruses. To evaluate poliovirus transmission, ES programs must be developed in a manner that is sensitive, with sufficiently frequent sampling, appropriate isolation methods, and specifically targeted sampling sites in locations at highest risk for poliovirus transmission. After poliovirus ceased to be detected in human cases, ES documented the absence of endemic WPV transmission and detected imported WPV. ES provides valuable information, particularly in high-density populations where AFP surveillance is of poor quality, persistent virus circulation is suspected, or frequent virus reintroduction is perceived. Given the benefits of ES, GPEI plans to continue and expand ES as part of its strategic plan and as a supplement to AFP surveillance.
Topics: Disease Eradication; Environmental Monitoring; Epidemiological Monitoring; Humans; Poliomyelitis; Poliovirus; Sewage
PubMed: 25316848
DOI: 10.1093/infdis/jiu384 -
Nature Medicine Oct 2018
Topics: Diabetes Mellitus, Type 2; Humans; Poliomyelitis; Poliovirus; Vaccines
PubMed: 30297892
DOI: 10.1038/s41591-018-0228-y -
The Journal of Infectious Diseases Sep 2021Both inactivated poliovirus vaccine (IPV) and oral poliovirus vaccine (OPV) have contributed to the rapid disappearance of paralytic poliomyelitis from developed...
Both inactivated poliovirus vaccine (IPV) and oral poliovirus vaccine (OPV) have contributed to the rapid disappearance of paralytic poliomyelitis from developed countries despite possessing different vaccine properties. Due to cost, ease of use, and other properties, the Expanded Programme on Immunization added OPV to the routine infant immunization schedule for low-income countries in 1974, but variable vaccine uptake and impaired immune responses due to poor sanitation limited the impact. Following launch of the Global Polio Eradication Initiative in 1988, poliomyelitis incidence has been reduced by >99% and types 2 and 3 wild polioviruses are now eradicated, but progress against type 1 polioviruses which are now confined to Afghanistan and Pakistan has slowed due to insecurity, poor access, and other problems. A strategic, globally coordinated replacement of trivalent OPV with bivalent 1, 3 OPV in 2016 reduced the incidence of vaccine-associated paralytic poliomyelitis (VAPP) but allowed the escape of type 2 vaccine-derived polioviruses (VDPV2) in areas with low immunization rates and use of monovalent OPV2 in response seeded new VDPV2 outbreaks and reestablishment of type 2 endemicity. A novel, more genetically stable type 2 OPV vaccine is undergoing clinical evaluation and may soon be deployed prevent or reduce VDPV2 emergences.
Topics: Disease Eradication; Global Health; Humans; Immunization Programs; Immunization Schedule; Infant; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Inactivated; Poliovirus Vaccine, Oral; Poliovirus Vaccines; Vaccination
PubMed: 34590135
DOI: 10.1093/infdis/jiaa622 -
Biochemical and Biophysical Research... Oct 2022Poliovirus (PV) can spread through neural pathway to the central nervous system and replicates in motor neurons, which leads to poliomyelitis. Enterovirus 71 (EV71),...
Poliovirus (PV) can spread through neural pathway to the central nervous system and replicates in motor neurons, which leads to poliomyelitis. Enterovirus 71 (EV71), which is closely related to PV, is one of the causative agents of hand-foot-and-mouth disease and can cause severe neurological diseases similar to poliomyelitis. Since PV is similar to EV71 in its motor neurotoxicity, we tried to understand if the results obtained with PV are of general applicability to EV71 and other viruses with similar characteristics. Using microfluidic devices, we demonstrated that both PV capsid and the PV genome undergo axonal retrograde transport with human PV receptor (hPVR), and the transported virus replicated in the soma of hPVR-expressing motor neurons. Similar to PV in hPVR-transgenic (Tg) mice, neural pathway ensuring spreading of EV71 has been shown in adult human scavenger receptor class B, member 2 (hSCARB2)-Tg mice. We have validated this finding in microfluidic devices by showing that EV71 is retrogradely transported together with hSCARB2 to the cell body where it replicates in an hSCARB2-dependent manner.
Topics: Animals; Axonal Transport; Enterovirus; Enterovirus A, Human; Humans; Mice; Mice, Transgenic; Motor Neurons; Poliomyelitis; Poliovirus
PubMed: 35973377
DOI: 10.1016/j.bbrc.2022.08.015 -
Viruses Sep 2019RNA recombination is a major driving force in the evolution and genetic architecture shaping of enteroviruses. In particular, intertypic recombination is implicated in... (Review)
Review
RNA recombination is a major driving force in the evolution and genetic architecture shaping of enteroviruses. In particular, intertypic recombination is implicated in the emergence of most pathogenic circulating vaccine-derived polioviruses, which have caused numerous outbreaks of paralytic poliomyelitis worldwide. Recent experimental studies that relied on recombination cellular systems mimicking natural genetic exchanges between enteroviruses provided new insights into the molecular mechanisms of enterovirus recombination and enabled to define a new model of genetic plasticity for enteroviruses. Homologous intertypic recombinant enteroviruses that were observed in nature would be the final products of a multi-step process, during which precursor nonhomologous recombinant genomes are generated through an initial inter-genomic RNA recombination event and can then evolve into a diversity of fitter homologous recombinant genomes over subsequent intra-genomic rearrangements. Moreover, these experimental studies demonstrated that the enterovirus genome could be defined as a combination of genomic modules that can be preferentially exchanged through recombination, and enabled defining the boundaries of these recombination modules. These results provided the first experimental evidence supporting the theoretical model of enterovirus modular evolution previously elaborated from phylogenetic studies of circulating enterovirus strains. This review summarizes our current knowledge regarding the mechanisms of recombination in enteroviruses and presents a new evolutionary process that may apply to other RNA viruses.
Topics: Animals; Enterovirus; Enterovirus Infections; Evolution, Molecular; Genome, Viral; Humans; Phylogeny; Poliovirus; Recombination, Genetic
PubMed: 31540135
DOI: 10.3390/v11090859 -
Journal of Clinical Microbiology Feb 2018With poliovirus eradication nearing, few pockets of active wild poliovirus (WPV) transmission remain in the world. Intratypic differentiation (ITD) plays a crucial part...
With poliovirus eradication nearing, few pockets of active wild poliovirus (WPV) transmission remain in the world. Intratypic differentiation (ITD) plays a crucial part in laboratory surveillance as the molecular detection method that can identify and distinguish wild and vaccine-like polioviruses isolated from acute flaccid paralysis cases or environmental sources. The need to detect new variants of WPV serotype 1 (WPV1) and the containment of all serotype 2 polioviruses (PV2) in 2015 required changes to the previous version of the method. The ITD version 5.0 is a set of six real-time reverse transcription-PCR (rRT-PCR) assays that serve as accurate diagnostic tools to easily detect and differentiate PV serotypes and genotypes. We describe the creation and properties of quantitation standards, including 16 control RNA transcripts and nine plaque-isolated viruses. All ITD rRT-PCR assays were validated using these standards, and the limits of detection were determined for each assay. We designed and pilot tested two new assays targeting recently circulating WPV1 genotypes and all PV2 viruses. The WPV1 assay had 99.1% specificity and 100% sensitivity, and the PV2 assay had 97.7% specificity and 92% sensitivity. Before proceeding to the next step in the global poliovirus eradication program, we needed to gain a better understanding of the performance of the ITD 5.0 suite of molecular assays and their limits of detection and specificities. The findings and conclusions in this evaluation serve as building blocks for future development work.
Topics: Disease Eradication; Epidemiological Monitoring; Genotype; Humans; Molecular Typing; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Oral; RNA, Viral; Reproducibility of Results; Reverse Transcriptase Polymerase Chain Reaction; Sensitivity and Specificity; Serogroup
PubMed: 29212703
DOI: 10.1128/JCM.01624-17