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The Journal of General Virology Jun 2023Enterovirus A71 (EVA71) causes widespread disease in young children with occasional fatal consequences. In common with other picornaviruses, both empty capsids (ECs) and...
Enterovirus A71 (EVA71) causes widespread disease in young children with occasional fatal consequences. In common with other picornaviruses, both empty capsids (ECs) and infectious virions are produced during the viral lifecycle. While initially antigenically indistinguishable from virions, ECs readily convert to an expanded conformation at moderate temperatures. In the closely related poliovirus, these conformational changes result in loss of antigenic sites required to elicit protective immune responses. Whether this is true for EVA71 remains to be determined and is the subject of this investigation.We previously reported the selection of a thermally resistant EVA71 genogroup B2 population using successive rounds of heating and passage. The mutations found in the structural protein-coding region of the selected population conferred increased thermal stability to both virions and naturally produced ECs. Here, we introduced these mutations into a recombinant expression system to produce stabilized virus-like particles (VLPs) in .The stabilized VLPs retain the native virion-like antigenic conformation as determined by reactivity with a specific antibody. Structural studies suggest multiple potential mechanisms of antigenic stabilization, however, unlike poliovirus, both native and expanded EVA71 particles elicited antibodies able to directly neutralize virus . Therefore, anti-EVA71 neutralizing antibodies are elicited by sites which are not canonically associated with the native conformation, but whether antigenic sites specific to the native conformation provide additional protective responses remains unclear. VLPs are likely to provide cheaper and safer alternatives for vaccine production and these data show that VLP vaccines are comparable with inactivated virus vaccines at inducing neutralising antibodies.
Topics: Child; Humans; Child, Preschool; Enterovirus; Enterovirus Infections; Antigens, Viral; Vaccines; Poliovirus; Antibodies, Viral
PubMed: 37390009
DOI: 10.1099/jgv.0.001867 -
Emerging Infectious Diseases Feb 2021Since May 2019, the Central African Republic has experienced a poliomyelitis outbreak caused by type 2 vaccine-derived polioviruses (VDPV-2s). The outbreak affected...
Since May 2019, the Central African Republic has experienced a poliomyelitis outbreak caused by type 2 vaccine-derived polioviruses (VDPV-2s). The outbreak affected Bangui, the capital city, and 10 districts across the country. The outbreak resulted from several independent emergence events of VDPV-2s featuring recombinant genomes with complex mosaic genomes. The low number of mutations (<20) in the viral capsid protein 1-encoding region compared with the vaccine strain suggests that VDPV-2 had been circulating for a relatively short time (probably <3 years) before being isolated. Environmental surveillance, which relies on a limited number of sampling sites in the Central African Republic and does not cover the whole country, failed to detect the circulation of VDPV-2s before some had induced poliomyelitis in children.
Topics: Central African Republic; Child; Disease Outbreaks; Humans; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Oral
PubMed: 33496226
DOI: 10.3201/eid2702.203173 -
Discovery Medicine May 2015Achieving tumor-specific, robust, and durable effector cytotoxic immune responses is key to successful immunotherapy. This has been accomplished with adoptive cell... (Review)
Review
Achieving tumor-specific, robust, and durable effector cytotoxic immune responses is key to successful immunotherapy. This has been accomplished with adoptive cell transfer of ex vivo-expanded autologous tumor-infiltrating or engineered T cells, or with immune checkpoint inhibitors, enhancing inherent T cell reactivity. A natural ability to recruit effector responses makes tumor-targeting ('oncolytic') viruses attractive as immunotherapy vehicles. However, most viruses actively block inflammatory and immunogenic events; or, host innate immune responses may prevent immune initiating events in the first place. Moreover, the mechanisms of how virus infection can produce effector responses against host (tumor) neo-antigens are unclear. We are pioneering oncolytic immunotherapy based on poliovirus, which has no specific mechanism to interfere with host immune activation, exhibits lytic cytotoxicity in the presence of an antiviral interferon response and pre-existing immunity, and engages a powerful innate immune sensor implicated in recruiting cytotoxic T cell responses. Central to this approach is a unique confluence of factors that drive tumor-specific viral translation and cytotoxicity.
Topics: Animals; Cytotoxicity, Immunologic; Humans; Immunotherapy; Neoplasms; Oncolytic Virotherapy; Oncolytic Viruses; Poliovirus
PubMed: 26105699
DOI: No ID Found -
Journal of Clinical Virology : the... Jun 2016Efficient implementation of the global eradication strategies consisting of Acute Flaccid Paralysis (AFP) surveillance and mass immunization campaigns led to...
BACKGROUND
Efficient implementation of the global eradication strategies consisting of Acute Flaccid Paralysis (AFP) surveillance and mass immunization campaigns led to interruption of indigenous wild poliovirus transmission in Cameroon in 1999.
OBJECTIVES
This study describes type 1 and type 3 wild poliovirus (WPV) importation, incidence, geographic distribution and control since the original interruption of transmission in Cameroon.
STUDY DESIGN
Stool samples from AFP patients under the age of 15 years in Cameroon were collected nationwide and subjected to virus isolation on RD and L20B cell cultures. Resulting virus isolates were typed by intratypic differentiation (ITD) and analysis of the VP1 coding sequence of the viral genome. Surveillance data originating from Cameroon between 2000 and 2014 were considered for retrospective descriptive analyses.
RESULTS
From 2003 to 2009, multiple WPV importation events from neighboring countries affected mainly in the northern regions of Cameroon but did not led to sustained local transmission. Throughout this period, 16 WPV1 and 5 WPV3 were detected and identified as members of multiple clusters within type-specific West Africa B genotypes (WEAF-B). In 2013-2014, a polio outbreak associated to a highly evolved ("orphan") WPV1 affected four southern regions of Cameroon.
CONCLUSIONS
The appearance of highly evolved lineage of type 1 WPV suggests potential surveillance gap and underscore the need to maintain comprehensive polio immunization activities and sensitive surveillance systems in place as long as any country in the world remains endemic for WPV.
Topics: Adolescent; Cameroon; Child; Child, Preschool; Disease Outbreaks; Disease Transmission, Infectious; Feces; Female; Genotype; Humans; Incidence; Infant; Infant, Newborn; Male; Poliomyelitis; Poliovirus; Retrospective Studies; Sequence Analysis, DNA; Topography, Medical; Travel
PubMed: 27045455
DOI: 10.1016/j.jcv.2016.03.025 -
Human Vaccines & Immunotherapeutics 2015The WHO European Region has been declared polio-free since 2002. By 2010, inactivated polio vaccine (IPV) was the only polio vaccine in use in the EU/EEA for the primary... (Review)
Review
The WHO European Region has been declared polio-free since 2002. By 2010, inactivated polio vaccine (IPV) was the only polio vaccine in use in the EU/EEA for the primary vaccination of children. A systematic review of the literature on polio seroprevalence studies, complemented by the analysis of available vaccine coverage data, has been carried out with the aim of assessing the level of protection against polio in the European population. A total of 52 studies, with data from 14 out of the 31 EU/EEA countries, were included in the analysis. This systematic review shows that, overall, seroprevalence for PV1 and PV3 is high in most countries, although seroimmunity gaps have been detected in several birth cohorts. In particular, relatively low immunity status was found in some countries for individuals born in the 60's and 70's. Discrepancies between reported vaccination coverage and immunity levels have been also highlighted. Countries should make sure that their population is being vaccinated for polio to reduce the risk of local poliovirus transmission in case of importation. Moreover, assessing immunity status should be priority for those traveling to areas where wild polioviruses are still circulating.
Topics: Antibodies, Viral; European Union; Humans; Poliomyelitis; Poliovirus; Seroepidemiologic Studies
PubMed: 25898095
DOI: 10.1080/21645515.2015.1016673 -
The New England Journal of Medicine Aug 2018Mass campaigns with oral poliovirus vaccine (OPV) have brought the world close to the eradication of wild poliovirus. However, to complete eradication, OPV must itself...
BACKGROUND
Mass campaigns with oral poliovirus vaccine (OPV) have brought the world close to the eradication of wild poliovirus. However, to complete eradication, OPV must itself be withdrawn to prevent outbreaks of vaccine-derived poliovirus (VDPV). Synchronized global withdrawal of OPV began with serotype 2 OPV (OPV2) in April 2016, which presented the first test of the feasibility of eradicating all polioviruses.
METHODS
We analyzed global surveillance data on the detection of serotype 2 Sabin vaccine (Sabin-2) poliovirus and serotype 2 vaccine-derived poliovirus (VDPV2, defined as vaccine strains that are at least 0.6% divergent from Sabin-2 poliovirus in the viral protein 1 genomic region) in stool samples from 495,035 children with acute flaccid paralysis in 118 countries and in 8528 sewage samples from four countries at high risk for transmission; the samples were collected from January 1, 2013, through July 11, 2018. We used Bayesian spatiotemporal smoothing and logistic regression to identify and map risk factors for persistent detection of Sabin-2 poliovirus and VDPV2.
RESULTS
The prevalence of Sabin-2 poliovirus in stool samples declined from 3.9% (95% confidence interval [CI], 3.5 to 4.3) at the time of OPV2 withdrawal to 0.2% (95% CI, 0.1 to 2.7) at 2 months after withdrawal, and the detection rate in sewage samples declined from 71.0% (95% CI, 61.0 to 80.0) to 13.0% (95% CI, 8.0 to 20.0) during the same period. However, 12 months after OPV2 withdrawal, Sabin-2 poliovirus continued to be detected in stool samples (<0.1%; 95% CI, <0.1 to 0.1) and sewage samples (8.0%; 95% CI, 5.0 to 13.0) because of the use of OPV2 in response to VDPV2 outbreaks. Nine outbreaks were reported after OPV2 withdrawal and were associated with low coverage of routine immunization (odds ratio, 1.64 [95% CI, 1.14 to 2.54] per 10% absolute decrease) and low levels of population immunity (odds ratio, 2.60 [95% CI, 1.35 to 5.59] per 10% absolute decrease) within affected countries.
CONCLUSIONS
High population immunity has facilitated the decline in the prevalence of Sabin-2 poliovirus after OPV2 withdrawal and restricted the circulation of VDPV2 to areas known to be at high risk for transmission. The prevention of VDPV2 outbreaks in these known areas before the accumulation of substantial cohorts of children susceptible to type 2 poliovirus remains a high priority. (Funded by the Bill and Melinda Gates Foundation and the World Health Organization.).
Topics: Adolescent; Africa; Asia; Child; Child, Preschool; Disease Eradication; Disease Outbreaks; Feces; Female; Humans; Infant; Infant, Newborn; Logistic Models; Male; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Inactivated; Poliovirus Vaccine, Oral; Population Surveillance; Serogroup; Sewage
PubMed: 30157398
DOI: 10.1056/NEJMoa1716677 -
Journal of Virology Jul 2015Picornavirus infection involves a dynamic interplay of host and viral protein interactions that modulates cellular processes to facilitate virus infection and evade host...
UNLABELLED
Picornavirus infection involves a dynamic interplay of host and viral protein interactions that modulates cellular processes to facilitate virus infection and evade host antiviral defenses. Here, using a proteomics-based approach known as TAILS to identify protease-generated neo-N-terminal peptides, we identify a novel target of the poliovirus 3C proteinase, the heterogeneous nuclear ribonucleoproteinM(hnRNP M), a nucleocytoplasmic shuttling RNA-binding protein that is primarily known for its role in pre-mRNA splicing. hnRNPMis cleaved in vitro by poliovirus and coxsackievirus B3 (CVB3) 3C proteinases and is targeted in poliovirus- and CVB3-infected HeLa cells and in the hearts of CVB3-infected mice. hnRNPMrelocalizes from the nucleus to the cytoplasm during poliovirus infection. Finally, depletion of hnRNPMusing small interfering RNA knockdown approaches decreases poliovirus and CVB3 infections in HeLa cells and does not affect poliovirus internal ribosome entry site translation and viral RNA stability. We propose that cleavage of and subverting the function of hnRNPMis a general strategy utilized by picornaviruses to facilitate viral infection.
IMPORTANCE
Enteroviruses, a member of the picornavirus family, are RNA viruses that cause a range of diseases, including respiratory ailments, dilated cardiomyopathy, and paralysis. Although enteroviruses have been studied for several decades, the molecular basis of infection and the pathogenic mechanisms leading to disease are still poorly understood. Here, we identify hnRNPMas a novel target of a viral proteinase. We demonstrate that the virus subverts the function of hnRNPMand redirects it to a step in the viral life cycle. We propose that cleavage of hnRNPMis a general strategy that picornaviruses use to facilitate infection.
Topics: 3C Viral Proteases; Animals; Cysteine Endopeptidases; Enterovirus B, Human; Enterovirus Infections; HeLa Cells; Heart; Heterogeneous-Nuclear Ribonucleoprotein Group M; Host-Pathogen Interactions; Humans; Mice; Myocardium; Poliovirus; Proteolysis; Viral Proteins
PubMed: 25926642
DOI: 10.1128/JVI.02977-14 -
The Lancet. Microbe Dec 2022Sabin strains used in oral poliovirus vaccines (OPV) can revert to virulence and, in rare instances, cause disease or generate vaccine-derived strains leading to...
Genetic and phenotypic stability of poliovirus shed from infants who received novel type 2 or Sabin type 2 oral poliovirus vaccines in Panama: an analysis of two clinical trials.
BACKGROUND
Sabin strains used in oral poliovirus vaccines (OPV) can revert to virulence and, in rare instances, cause disease or generate vaccine-derived strains leading to outbreaks in areas of low immunisation coverage. A novel OPV2 (nOPV2) was designed to stabilise the viral genome against reversion and reduce recombination events that might lead to virulent strains. In this study, we evaluated the genetic and phenotypic stability of shed poliovirus following administration of one dose of monovalent OPV2 (mOPV2) or nOPV2 to infants aged 18-22 weeks.
METHODS
In two similarly designed clinical trials (NCT02521974 and NCT03554798) conducted in Panama, infants aged 18-22-weeks, after immunisation with three doses of bivalent OPV (types 1 and 3) and one dose of inactivated poliovirus vaccine, were administered one or two doses of mOPV2 or nOPV2. In this analysis of two clinical trials, faecally shed polioviruses following one dose of mOPV2 or nOPV2 were isolated from stools meeting predetermined criteria related to sample timing and viral presence and quantity and assessed for nucleotide polymorphisms using next-generation sequencing. A transgenic mouse neurovirulence test was adapted to assess the effect of the possible phenotypic reversion of shed mOPV2 and nOPV2 with a logistic regression model.
FINDINGS
Of the 91 eligible samples, 86 were able to be sequenced, with 72 evaluated in the transgenic mouse assay. Sabin-2 poliovirus reverts rapidly at nucleotide 481, the primary attenuation site in domain V of the 5' untranslated region of the genome. There was no evidence of neurovirulence-increasing polymorphisms in domain V of shed nOPV2. Reversion of shed Sabin-2 virus corresponded with unadjusted paralysis rates of 47·6% at the 4 log 50% cell culture infectious dose (CCID) and 76·7% at the 5 log CCID inoculum levels, with rates of 2·8% for 4 log CCID and 11·8% for 5 log CCID observed for shed nOPV2 samples. The estimated adjusted odds ratio at 4·5 log of 0·007 (95% CI 0·002-0·023; p<0·0001) indicates significantly reduced odds of mouse paralysis from virus obtained from nOPV2 recipients compared with mOPV2 recipients.
INTERPRETATION
The data indicate increased genetic stability of domain V of nOPV2 relative to mOPV2, with significantly lower neurovirulence of shed nOPV2 virus compared with shed mOPV2. While this vaccine is currently being deployed under an emergency use listing, the data on the genetic stability of nOPV2 will support further regulatory and policy decision-making regarding use of nOPV2 in outbreak responses.
FUNDING
Bill & Melinda Gates Foundation.
Topics: Mice; Animals; Poliovirus; Poliomyelitis; Poliovirus Vaccine, Oral; 5' Untranslated Regions; Mice, Transgenic; Paralysis; Nucleotides
PubMed: 36332645
DOI: 10.1016/S2666-5247(22)00254-3 -
MSphere Apr 2019Several viruses encounter various bacterial species within the host and in the environment. Despite these close encounters, the effects of bacteria on picornaviruses are...
Several viruses encounter various bacterial species within the host and in the environment. Despite these close encounters, the effects of bacteria on picornaviruses are not completely understood. Previous work determined that poliovirus (PV), an enteric virus, has enhanced virion stability when exposed to bacteria or bacterial surface polysaccharides such as lipopolysaccharide. Virion stabilization by bacteria may be important for interhost transmission, since a mutant PV with reduced bacterial binding had a fecal-oral transmission defect in mice. Therefore, we investigated whether bacteria broadly enhance stability of picornaviruses from three different genera: (PV and coxsackievirus B3 [CVB3]), (Aichi virus), and (mengovirus). Furthermore, to delineate strain-specific effects, we examined two strains of CVB3 and a PV mutant with enhanced thermal stability. We determined that specific bacterial strains enhance thermal stability of PV and CVB3, while mengovirus and Aichi virus are stable at high temperatures in the absence of bacteria. Additionally, we determined that bacteria or lipopolysaccharide can stabilize PV, CVB3, Aichi virus, and mengovirus during exposure to bleach. These effects are likely mediated through direct interactions with bacteria, since viruses bound to bacteria in a pulldown assay. Overall, this work reveals shared and distinct effects of bacteria on a panel of picornaviruses. Recent studies have shown that bacteria promote infection and stabilization of poliovirus particles, but the breadth of these effects on other members of the family is unknown. Here, we compared the effects of bacteria on four distinct members of the family. We found that bacteria reduced inactivation of all of the viruses during bleach treatment, but not all viral strains were stabilized by bacteria during heat treatment. Overall, our data provide insight into how bacteria play differential roles in picornavirus stability.
Topics: Bacteria; Cardiovirus; Enterovirus; Hot Temperature; Kobuvirus; Microbial Interactions; Mutation; Picornaviridae; Poliovirus; Sodium Hypochlorite; Virus Inactivation
PubMed: 30944213
DOI: 10.1128/mSphere.00183-19 -
Viruses Jul 2021The oral poliovirus vaccine (OPV), which prevents person-to-person transmission of poliovirus by inducing robust intestinal immunity, has been a crucial tool for global... (Review)
Review
The oral poliovirus vaccine (OPV), which prevents person-to-person transmission of poliovirus by inducing robust intestinal immunity, has been a crucial tool for global polio eradication. However, polio outbreaks, mainly caused by type 2 circulating vaccine-derived poliovirus (cVDPV2), are increasing worldwide. Meanwhile, immunodeficiency-associated vaccine-derived poliovirus (iVDPV) is considered another risk factor during the final stage of global polio eradication. Patients with primary immunodeficiency diseases are associated with higher risks for long-term iVDPV infections. Although a limited number of chronic iVDPV excretors were reported, the recent identification of a chronic type 2 iVDPV (iVDPV2) excretor in the Philippines highlights the potential risk of inapparent iVDPV infection for expanding cVDPV outbreaks. Further research on the genetic characterizations and molecular evolution of iVDPV2, based on comprehensive iVDPV surveillance, will be critical for elucidating the remaining risk of iVDPV2 during the post-OPV era.
Topics: Disease Eradication; Disease Outbreaks; Evolution, Molecular; Global Health; Humans; Immunocompromised Host; Poliovirus; Poliovirus Vaccine, Oral; Primary Immunodeficiency Diseases; Vaccination
PubMed: 34372613
DOI: 10.3390/v13071407