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1.
Geospat Health ; 17(2)2022 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-36468597

RESUMO

Afghanistan continues to experience challenges affecting polio eradication. Mass polio vaccination campaigns, which aim to protect children under the age of 5, are a key eradication strategy. To date, the polio program in Afghanistan has only employed facility-based seroprevalence surveys, which can be subject to sampling bias. We describe the feasibility in implementing a cross-sectional household poliovirus seroprevalence survey based on geographical information systems (GIS) in three districts. Digital maps with randomly selected predetermined starting points were provided to teams, with a total target of 1,632 households. Teams were instructed to navigate to predetermined starting points and enrol the closest household within 60 m. To assess effectiveness of these methods, we calculated percentages for total households enrolled with valid geocoordinates collected within the designated boundary, and whether the Euclidean distance of households were within 60 m of a predetermined starting point. A normalized difference vegetation index (NDVI) image ratio was conducted to further investigate variability in team performances. The study enrolled a total of 78% of the target sample with 52% of all households within 60 m of a pre-selected point and 79% within the designated cluster boundary. Success varied considerably between the four target areas ranging from 42% enrolment of the target sample in one place to 90% enrolment of the target sample in another. Interviews with the field teams revealed that differences in security status and amount of non-residential land cover were key barriers to higher enrolment rates. Our findings indicate household poliovirus seroprevalence surveys using GIS-based sampling can be effectively implemented in polio endemic countries to capture representative samples. We also proposed ways to achieve higher success rates if these methods are to be used in the future, particularly in areas with concerns of insecurity or spatially dispersed residential units.


Assuntos
Poliomielite , Poliovirus , Criança , Humanos , Sistemas de Informação Geográfica , Afeganistão/epidemiologia , Estudos Transversais , Estudos Soroepidemiológicos , Poliomielite/epidemiologia , Poliomielite/prevenção & controle
2.
MMWR Morb Mortal Wkly Rep ; 71(44): 1418-1424, 2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36327157

RESUMO

In July 2022, a case of paralytic poliomyelitis resulting from infection with vaccine-derived poliovirus (VDPV) type 2 (VDPV2)§ was confirmed in an unvaccinated adult resident of Rockland County, New York (1). As of August 10, 2022, poliovirus type 2 (PV2)¶ genetically linked to this VDPV2 had been detected in wastewater** in Rockland County and neighboring Orange County (1). This report describes the results of additional poliovirus testing of wastewater samples collected during March 9-October 11, 2022, and tested as of October 20, 2022, from 48 sewersheds (the community area served by a wastewater collection system) serving parts of Rockland County and 12 surrounding counties. Among 1,076 wastewater samples collected, 89 (8.3%) from 10 sewersheds tested positive for PV2. As part of a broad epidemiologic investigation, wastewater testing can provide information about where poliovirus might be circulating in a community in which a paralytic case has been identified; however, the most important public health actions for preventing paralytic poliomyelitis in the United States remain ongoing case detection through national acute flaccid myelitis (AFM) surveillance†† and improving vaccination coverage in undervaccinated communities. Although most persons in the United States are sufficiently immunized, unvaccinated or undervaccinated persons living or working in Kings, Orange, Queens, Rockland, or Sullivan counties, New York should complete the polio vaccination series as soon as possible.


Assuntos
Poliomielite , Vacina Antipólio Oral , Poliovirus , Adulto , Humanos , New York/epidemiologia , Poliomielite/diagnóstico , Poliomielite/epidemiologia , Poliomielite/prevenção & controle , Poliovirus/genética , Vacina Antipólio Oral/efeitos adversos , Estados Unidos , Águas Residuárias
3.
BMC Infect Dis ; 22(1): 821, 2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36348312

RESUMO

BACKGROUND: Poliomyelitis outbreaks due to pathogenic vaccine-derived polioviruses (VDPVs) are threatening and complicating the global polio eradication initiative. Most of these VDPVs are genetic recombinants with non-polio enteroviruses (NPEVs) of species C. Little is known about factors favoring this genetic macroevolution process. Since 2001, Madagascar has experienced several outbreaks of poliomyelitis due to VDPVs, and most of VDPVs were isolated in the south of the island. The current study explored some of the viral factors that can promote and explain the emergence of recombinant VDPVs in Madagascar. METHODS: Between May to August 2011, we collected stools from healthy children living in two southern and two northern regions of Madagascar. Virus isolation was done in RD, HEp-2c, and L20B cell lines, and enteroviruses were detected using a wide-spectrum 5'-untranslated region RT-PCR assay. NPEVs were then sequenced for the VP1 gene used for viral genotyping. RESULTS: Overall, we collected 1309 stools, of which 351 NPEVs (26.8%) were identified. Sequencing revealed 33 types of viruses belonging to three different species: Enterovirus A (8.5%), Enterovirus B (EV-B, 40.2%), and Enterovirus C (EV-C, 51.3%). EV-C species included coxsackievirus A13, A17, and A20 previously described as putative recombination partners for poliovirus vaccine strains. Interestingly, the isolation rate was higher among stools originating from the South (30.3% vs. 23.6%, p-value = 0.009). EV-C were predominant in southern sites (65.7%) while EV-B predominated in northern sites (54.9%). The factors that explain the relative abundance of EV-C in the South are still unknown. CONCLUSIONS: Whatever its causes, the relative abundance of EV-C in the South of Madagascar may have promoted the infections of children by EV-C, including the PV vaccine strains, and have favored the recombination events between PVs and NPEVs in co-infected children, thus leading to the recurrent emergence of recombinant VDPVs in this region of Madagascar.


Assuntos
Enterovirus Humano C , Infecções por Enterovirus , Enterovirus , Poliomielite , Vacinas contra Poliovirus , Poliovirus , Criança , Humanos , Madagáscar/epidemiologia , Filogenia , Infecções por Enterovirus/epidemiologia , Poliomielite/prevenção & controle , Enterovirus Humano C/genética , Surtos de Doenças , Vacina Antipólio Oral/efeitos adversos
4.
Lancet Microbe ; 3(12): e912-e921, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36332645

RESUMO

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 log10 50% cell culture infectious dose (CCID50) and 76·7% at the 5 log10 CCID50 inoculum levels, with rates of 2·8% for 4 log10 CCID50 and 11·8% for 5 log10 CCID50 observed for shed nOPV2 samples. The estimated adjusted odds ratio at 4·5 log10 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.


Assuntos
Poliomielite , Poliovirus , Camundongos , Animais , Poliovirus/genética , Poliomielite/prevenção & controle , Vacina Antipólio Oral , Regiões 5' não Traduzidas , Camundongos Transgênicos , Paralisia , Nucleotídeos
5.
Commun Biol ; 5(1): 1293, 2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36434067

RESUMO

Strategies to prevent the recurrence of poliovirus (PV) after eradication may utilise non-infectious, recombinant virus-like particle (VLP) vaccines. Despite clear advantages over inactivated or attenuated virus vaccines, instability of VLPs can compromise their immunogenicity. Glutathione (GSH), an important cellular reducing agent, is a crucial co-factor for the morphogenesis of enteroviruses, including PV. We report cryo-EM structures of GSH bound to PV serotype 3 VLPs showing that it can enhance particle stability. GSH binds the positively charged pocket at the interprotomer interface shown recently to bind GSH in enterovirus F3 and putative antiviral benzene sulphonamide compounds in other enteroviruses. We show, using high-resolution cryo-EM, the binding of a benzene sulphonamide compound with a PV serotype 2 VLP, consistent with antiviral activity through over-stabilizing the interprotomer pocket, preventing the capsid rearrangements necessary for viral infection. Collectively, these results suggest GSH or an analogous tight-binding antiviral offers the potential for stabilizing VLP vaccines.


Assuntos
Enterovirus , Poliovirus , Vacinas de Partículas Semelhantes a Vírus , Poliovirus/metabolismo , Antivirais/farmacologia , Benzeno , Sítios de Ligação , Antígenos Virais , Glutationa/metabolismo , Sulfonamidas
6.
Lancet Glob Health ; 10(12): e1807-e1814, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36400086

RESUMO

BACKGROUND: Novel oral poliovirus vaccine type 2 (nOPV2) was used to control an outbreak of type 2 circulating vaccine derived poliovirus (cVDPV2) in Tajikistan, in 2021. We measured seroconversion and seroprevalence of type 2 polio antibodies in children who were reported to have received two doses of nOPV2 in outbreak response campaigns. METHODS: In this community serosurvey, children born after Jan 1, 2016 were enrolled from seven districts in Tajikistan. Dried blood spot cards were collected before nOPV2 campaigns and after the first and second rounds of the campaigns and were sent to the Centers for Disease Control and Prevention (Atlanta, GA, USA) for microneutralisation assay to determine presence of polio antibodies. The primary endpoint was to assess change in seroprevalence and seroconversion against poliovirus serotype 2 after one and two doses of nOPV2. FINDINGS: 228 (97%) of 236 enrolled children were included in the analysis. The type 2 antibody seroprevalence was 26% (53/204; 95% CI 20 to 33) before nOPV2, 77% (161/210; 70 to 82) after one dose of nOPV2, and 83% (174/209; 77 to 88) after two doses of nOPV2. The increase in seroprevalence was statistically significant between baseline and after one nOPV2 dose (51 percentage points [42 to 59], p<0·0001), but not between the first and second doses (6 percentage points [-2 to 15], p=0·12). Seroconversion from the first nOPV2 dose, 67% (89/132; 59 to 75), was significantly greater than that from the second nOPV2 dose, 44% (20/45; 30 to 60; χ2 p=0·010). Total seroconversion after two nOPV2 doses was 77% (101/132; 68 to 83). INTERPRETATION: Our study demonstrated strong immune responses following nOPV2 outbreak response campaigns in Tajikistan. Our results support previous clinical trial data on the generation of poliovirus type 2 immunity by nOPV2 and provide evidence that nOPV2 can be appropriate for the cVDPV2 outbreak response. The licensure and WHO prequalification of nOPV2 should be accelerated to facilitate wider use of the vaccine. FUNDING: World Health Organization, Centers for Disease Control and Prevention, and Rotary International.


Assuntos
Poliomielite , Poliovirus , Criança , Humanos , Vacina Antipólio Oral , Estudos Soroepidemiológicos , Tadjiquistão/epidemiologia , Anticorpos Antivirais , Poliomielite/epidemiologia , Poliomielite/prevenção & controle , Programas de Imunização
9.
MMWR Morb Mortal Wkly Rep ; 71(42): 1313-1318, 2022 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-36264783

RESUMO

After reporting a single wild poliovirus (WPV) type 1 (WPV1) case in 2021, Pakistan reported 14 cases during April 1-July 31, 2022. Pakistan and Afghanistan are the only countries where endemic WPV transmission has never been interrupted (1). In its current 5-year strategic plan, the Global Polio Eradication Initiative (GPEI) has set a goal of interrupting all WPV1 transmission by the end of 2023 (1-3). The reemergence of WPV cases in Pakistan after 14 months with no case detection has uncovered transmission in southern Khyber Pakhtunkhwa province, the most historically challenging area. This report describes Pakistan's progress toward polio eradication during January 2021-July 2022 and updates previous reports (4,5). As of August 20, 2022, all but one of the 14 WPV1 cases in Pakistan during 2022 have been reported from North Waziristan district in Khyber Pakhtunkhwa. In underimmunized populations, excretion of vaccine virus can, during a period of 12-18 months, lead to reversion to neurovirulence, resulting in circulating vaccine-derived polioviruses (cVDPVs), which can cause paralysis and outbreaks. An outbreak of cVDPV type 2 (cVDPV2), which began in Pakistan in 2019, has been successfully contained; the last case occurred in April 2021 (1,6). Despite program improvements, 400,000-500,000 children continue to be missed during nationwide polio supplementary immunization activities (SIAs),* and recent isolation of poliovirus from sewage samples collected in other provinces suggests wider WPV1 circulation during the ongoing high transmission season. Although vaccination efforts have been recently complicated by months of flooding during the summer of 2022, to successfully interrupt WPV1 transmission in the core reservoirs in southern Khyber Pakhtunkhwa and reach the GPEI goal, emphasis should be placed on further improving microplanning and supervision of SIAs and on systematic tracking and vaccination of persistently missed children in these reservoir areas of Pakistan.


Assuntos
Poliomielite , Poliovirus , Criança , Humanos , Erradicação de Doenças , Paquistão/epidemiologia , Esgotos , Programas de Imunização , Vigilância da População , Poliomielite/epidemiologia , Poliomielite/prevenção & controle , Vacina Antipólio Oral
10.
Viruses ; 14(10)2022 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-36298714

RESUMO

Following the success of global vaccination programmes using the live-attenuated oral and inactivated poliovirus vaccines (OPV and IPV), wild poliovirus (PV) is now only endemic in Afghanistan and Pakistan. However, the continued use of these vaccines poses potential risks to the eradication of PV. The production of recombinant PV virus-like particles (VLPs), which lack the viral genome offer great potential as next-generation vaccines for the post-polio world. We have previously reported production of PV VLPs using Pichia pastoris, however, these VLPs were in the non-native conformation (C Ag), which would not produce effective protection against PV. Here, we build on this work and show that it is possible to produce wt PV-3 and thermally stabilised PV-3 (referred to as PV-3 SC8) VLPs in the native conformation (D Ag) using Pichia pastoris. We show that the PV-3 SC8 VLPs provide a much-improved D:C antigen ratio as compared to wt PV-3, whilst exhibiting greater thermostability than the current IPV vaccine. Finally, we determine the cryo-EM structure of the yeast-derived PV-3 SC8 VLPs and compare this to previously published PV-3 D Ag structures, highlighting the similarities between these recombinantly expressed VLPs and the infectious virus, further emphasising their potential as a next-generation vaccine candidate for PV.


Assuntos
Poliomielite , Vacinas contra Poliovirus , Poliovirus , Humanos , Anticorpos Antivirais , Poliovirus/genética , Vacina Antipólio Oral
11.
Viruses ; 14(10)2022 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-36298811

RESUMO

Ficus rubiginosa plant extract showed antimicrobial activity, but no evidence concerning its antiviral properties was reported. The antiviral activity of the methanolic extract (MeOH) and its n-hexane (H) and ethyl acetate (EA) fractions against Herpes simplex virus-1 (HSV-1), Human coronavirus (HCoV) -229E, and Poliovirus-1 (PV-1) was investigated in the different phases of viral infection in the VERO CCL-81 cell line. To confirm the antiviral efficacy, a qPCR was conducted. The recorded cytotoxic concentration 50% was 513.1, 298.6, and 56.45 µg/mL for MeOH, H, and EA, respectively, assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay after 72 h of treatment. The Ficus rubiginosa leaf extract inhibited the replication of HSV-1 in the early stages of infection, showing a complete inhibition up to 0.62, 0.31, and 1.25 µg/mL. Against HCoV-229E, a total inhibition up to 1.25 µg/mL for MeOH and H as well as 5 µg/mL for EA was observed. Otherwise, no activity was recorded against PV-1. The leaf extract could act directly on the viral envelope, destructuring the lipid membrane and/or directly blocking the enriched proteins on the viral surface. The verified gene inhibition suggested that the treatments with M, H, and EA impaired HSV-1 and HCoV-229E replication, with a greater antiviral efficiency against HSV-1 compared to HCoV-229E, possibly due to a greater affinity of Ficus rubiginosa towards membrane glycoproteins and/or the different lipid envelopes.


Assuntos
Coronavirus Humano 229E , Ficus , Herpesvirus Humano 1 , Poliovirus , Humanos , Antivirais/farmacologia , Brometos , Extratos Vegetais/farmacologia , Glicoproteínas de Membrana , Lipídeos
12.
J Cell Biol ; 221(11)2022 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-36305789

RESUMO

Viruses co-opt host proteins to carry out their lifecycle. Repurposed host proteins may thus become functionally compromised; a situation analogous to a loss-of-function mutation. We term such host proteins as viral-induced hypomorphs. Cells bearing cancer driver loss-of-function mutations have successfully been targeted with drugs perturbing proteins encoded by the synthetic lethal (SL) partners of cancer-specific mutations. Similarly, SL interactions of viral-induced hypomorphs can potentially be targeted as host-based antiviral therapeutics. Here, we use GBF1, which supports the infection of many RNA viruses, as a proof-of-concept. GBF1 becomes a hypomorph upon interaction with the poliovirus protein 3A. Screening for SL partners of GBF1 revealed ARF1 as the top hit, disruption of which selectively killed cells that synthesize 3A alone or in the context of a poliovirus replicon. Thus, viral protein interactions can induce hypomorphs that render host cells selectively vulnerable to perturbations that leave uninfected cells otherwise unscathed. Exploiting viral-induced vulnerabilities could lead to broad-spectrum antivirals for many viruses, including SARS-CoV-2.


Assuntos
Fatores de Troca do Nucleotídeo Guanina , Poliovirus , Proteínas do Core Viral , Humanos , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Mutações Sintéticas Letais , Replicação Viral , Regulação Viral da Expressão Gênica , Proteínas do Core Viral/genética , Proteínas do Core Viral/metabolismo , Interações Hospedeiro-Patógeno
14.
Front Public Health ; 10: 990042, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36211670

RESUMO

Background: It is necessary to select suitable inactivated poliovirus vaccine(IPV) and live, attenuated oral poliovirus vaccine (OPV) sequential immunization programs and configure the corresponding health resources. An economic evaluation was conducted on the sequential procedures of Sabin strain-based IPV (sIPV) and bivalent OPV (bOPV) with different doses to verify whether a cost-effectiveness target can be achieved. This study aimed to evaluate the cost-effectiveness of different sIPV immunization schedules, which would provide convincing evidence to further change the poliovirus vaccine (PV) immunization strategies in China. Methods: Five strategies were included in this analysis. Based on Strategy 0(S0), the incremental cost (IC), incremental effect (IE), and incremental cost-effectiveness ratio (ICER) of the four different strategies (S1/S2/S3/S4) were calculated based on the perspective of the society. Seven cost items were included in this study. Results of field investigations and expert consultations were used to calculate these costs. Results: The ICs of S1/S2/S3/S4 was Chinese Yuan (CNY) 30.77, 68.58, 103.82, and 219.82 million, respectively. The IE of vaccine-associated paralytic poliomyelitis (IEVAPP) cases of S1/S2/S3/S4 were 0.22, 0.22, 0.22, and 0.11, respectively, while the IE of disability-adjusted life-years (IEDALY) of S1/S2/S3/S4 were 8.98, 8.98, 8.98, and 4.49, respectively. The ICERVAPP of S1/S2/S3/S4 gradually increased to CNY 13.99, 31.17, 47.19, and 199.83 million/VAPP, respectively. The ICERDALY of S1/S2/S3/S4 also gradually increased to CNY 0.34, 0.76, 1.16, and 4.90 million/DALY, respectively. Conclusion: ICERVAPP and ICERDALY were substantially higher for S3 (four-sIPV) and S4 (replacement of self-funded sIPV based on one-sIPV-three-bOPV). Two-sIPV-two-bOPV had a cost-effectiveness advantage, whereas S2/S3/S4 had no cost-effectiveness advantage.


Assuntos
Poliomielite , Poliovirus , Análise Custo-Benefício , Humanos , Esquemas de Imunização , Poliomielite/prevenção & controle , Vacina Antipólio de Vírus Inativado , Vacina Antipólio Oral
15.
Nat Commun ; 13(1): 5986, 2022 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-36216808

RESUMO

Enteroviruses are non-enveloped positive-sense RNA viruses that cause diverse diseases in humans. Their rapid multiplication depends on remodeling of cytoplasmic membranes for viral genome replication. It is unknown how virions assemble around these newly synthesized genomes and how they are then loaded into autophagic membranes for release through secretory autophagy. Here, we use cryo-electron tomography of infected cells to show that poliovirus assembles directly on replication membranes. Pharmacological untethering of capsids from membranes abrogates RNA encapsidation. Our data directly visualize a membrane-bound half-capsid as a prominent virion assembly intermediate. Assembly progression past this intermediate depends on the class III phosphatidylinositol 3-kinase VPS34, a key host-cell autophagy factor. On the other hand, the canonical autophagy initiator ULK1 is shown to restrict virion production since its inhibition leads to increased accumulation of virions in vast intracellular arrays, followed by an increased vesicular release at later time points. Finally, we identify multiple layers of selectivity in virus-induced autophagy, with a strong selection for RNA-loaded virions over empty capsids and the segregation of virions from other types of autophagosome contents. These findings provide an integrated structural framework for multiple stages of the poliovirus life cycle.


Assuntos
Infecções por Enterovirus , Poliovirus , Autofagia , Capsídeo , Classe III de Fosfatidilinositol 3-Quinases , Humanos , Poliovirus/genética , RNA , Vírion/genética , Montagem de Vírus/fisiologia
16.
PLoS Pathog ; 18(10): e1010906, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36306280

RESUMO

As ultimate parasites, viruses depend on host factors for every step of their life cycle. On the other hand, cells evolved multiple mechanisms of detecting and interfering with viral replication. Yet, our understanding of the complex ensembles of pro- and anti-viral factors is very limited in virtually every virus-cell system. Here we investigated the proteins recruited to the replication organelles of poliovirus, a representative of the genus Enterovirus of the Picornaviridae family. We took advantage of a strict dependence of enterovirus replication on a host protein GBF1, and established a stable cell line expressing a truncated GBF1 fused to APEX2 peroxidase that effectively supported viral replication upon inhibition of the endogenous GBF1. This construct biotinylated multiple host and viral proteins on the replication organelles. Among the viral proteins, the polyprotein cleavage intermediates were overrepresented, suggesting that the GBF1 environment is linked to viral polyprotein processing. The proteomics characterization of biotinylated host proteins identified multiple proteins previously associated with enterovirus replication, as well as more than 200 new factors recruited to the replication organelles. RNA metabolism proteins, many of which normally localize in the nucleus, constituted the largest group, underscoring the massive release of nuclear factors into the cytoplasm of infected cells and their involvement in viral replication. Functional analysis of several newly identified proteins revealed both pro- and anti-viral factors, including a novel component of infection-induced stress granules. Depletion of these proteins similarly affected the replication of diverse enteroviruses indicating broad conservation of the replication mechanisms. Thus, our data significantly expand the knowledge of the composition of enterovirus replication organelles, provide new insights into viral replication, and offer a novel resource for identifying targets for anti-viral interventions.


Assuntos
Infecções por Enterovirus , Enterovirus , Poliovirus , Humanos , Enterovirus/metabolismo , Biotinilação , Poliovirus/fisiologia , Replicação Viral , Proteínas Virais/metabolismo , Poliproteínas/metabolismo , Antivirais/farmacologia , Fatores de Troca do Nucleotídeo Guanina/metabolismo
17.
Artigo em Inglês | MEDLINE | ID: mdl-36276175

RESUMO

Objective: In response to an outbreak of circulating vaccine-derived poliovirus (cVDPV) type 2 in the Philippines in 2019-2020, several rounds of supplementary immunization activities using the monovalent type 2 oral poliovirus vaccine (OPV) were conducted for the first time in the Western Pacific Region. After use of the monovalent vaccine, the emergence of vaccine-derived poliovirus unrelated to the outbreak virus was detected in healthy children and environmental samples. This report describes the detection of this poliovirus in the Philippines after use of the monovalent type 2 OPV for outbreak response. Methods: We describe the emergence of vaccine-derived poliovirus unrelated to the outbreak detected after supplementary immunization activities using the monovalent type 2 OPV. This analysis included virus characterization, phylogenetic analyses and epidemiological investigations. Results: Three environmental samples and samples from six healthy children tested positive for the emergent vaccine-derived poliovirus. All isolates differed from the Sabin type 2 reference strain by 6-13 nucleotide changes, and all were detected in the National Capital Region and Region 4, which had conducted supplementary immunization activities. Discussion: Since the 2016 removal of type 2 strains from the OPV, vaccine-derived poliovirus outbreaks have occurred in communities that are immunologically naive to poliovirus type 2 and in areas with recent use of monovalent OPV. To prevent the emergence and further spread of cVDPV type 2, several interventions could be implemented including optimizing outbreak responses by using the monovalent type 2 OPV, accelerating the availability of the novel type 2 OPV, strengthening routine immunization using inactivated polio vaccine and eventually replacing OPV with inactivated poliovirus vaccine for routine immunization.


Assuntos
Poliomielite , Poliovirus , Criança , Humanos , Vacina Antipólio Oral/efeitos adversos , Vacina Antipólio de Vírus Inativado , Poliomielite/epidemiologia , Poliomielite/prevenção & controle , Filogenia , Filipinas/epidemiologia , Surtos de Doenças , Nucleotídeos
18.
Vaccine ; 40(47): 6802-6805, 2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36244880

RESUMO

Polio, or poliomyelitis, is a disabling and life-threatening disease caused by three poliovirus (PV) serotypes. The virus spreads from person to person and can infect a person's spinal cord, causing paralysis. In 1988, when the WHO registered 350,000 cases of poliomyelitis in the world and 70,000 which occurred in Africa alone, global poliomyelitis eradication was proposed by the World Health Organization to its member States. On 25 August 2020, while the world was waging war against the Coronavirus pandemic, a historic milestone was reached: Africa was officially declared polio-free. It is an important result obtained thanks to an intensive large-scale vaccination campaign. The road was far from smooth, nevertheless, according to the WHO, a great effort needs to be made in order to facilitate access to vaccination and to promote its implementation in those countries where coverage is low and vaccine hesitancy is high because the risk of the spread of poliomyelitis is still relevant. Eradication of the virus in Africa provides us with an excellent opportunity to commemorate the many scientists who contributed to achieving this epoch-making goal: first of all, Jonas Salk, who developed a killed-virus vaccine in 1952, and, especially, Albert Sabin, who in 1961 launched programs of mass immunisation with his oral vaccine against poliomyelitis.


Assuntos
Poliomielite , Poliovirus , Criança , Humanos , Vacina Antipólio Oral , Poliomielite/prevenção & controle , Vacina Antipólio de Vírus Inativado , Vacinação em Massa
19.
Brasília, D.F.; OPAS; 2022-10-19.
Não convencional em Português | PAHO-IRIS | ID: phr2-56561

RESUMO

A promessa de um mundo livre da poliomielite tem sido a força motriz por trás da Iniciativa Global de Erradicação da Poliomielite (GPEI), contribuindo para ganhos fundamentais na saúde nas últimas três décadas. De fato, antes da doença do coronavírus (COVID-19), a erradicação da poliomielite significava para muitos algo que o mundo poderia alcançar unindo-se para proteger e promover a saúde de todas as crianças. Ao longo da última década, a Iniciativa Global de Erradicação da Poliomielite (GPEI) fez progressos constantes no caminho para a erradicação. Os poliovírus selvagens tipos 2 e 3 (WPV2 e WPV3) foram declarados erradicados em 2015 e 2019, respectivamente; a Região da Organização Mundial da Saúde (OMS) do Sudeste Asiático foi declarada livre de poliovírus em 2014; e, mais recentemente, a Região Africana da OMS foi certificada como livre de poliovírus selvagem (WPV) em agosto de 2020. No entanto, os passos finais para a erradicação provaram ser os mais difíceis. A Estratégia de Erradicação da Poliomielite 2022-2026 compreende um amplo conjunto de ações a fim de posicionar a GPEI para cumprir uma promessa que uniu o mundo em um compromisso coletivo de erradicação da poliomielite. Essas ações, muitas das quais já estavam em andamento em 2021, fortalecerão e capacitarão a GPEI para enfrentar os problemas, alcançar e manter um mundo livre da poliomielite.


Assuntos
Poliomielite , Poliovirus , Vacinas contra Poliovirus , Doenças Preveníveis por Vacina , COVID-19
20.
Jpn J Infect Dis ; 75(5): 431-444, 2022 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-36047174

RESUMO

The World Health Organization Western Pacific Region (WPR) has maintained a polio-free status for more than two decades. At the global level, there were only six confirmed polio cases due to wild type 1 poliovirus in Pakistan, Afghanistan, and Malawi in 2021; therefore, the risk of wild poliovirus importation from endemic countries to the WPR is considerably lower than that in the past. However, the risk of polio outbreaks associated with circulating vaccine-derived polioviruses (cVDPVs) cannot be ignored even in the WPR. Since the late 2010s, cVDPV outbreaks in the WPR have increased in frequency and magnitude. Moreover, the emergence of concomitant polio outbreaks of type 1 and type 2 cVDPVs in the Philippines and Malaysia during 2019-2020 highlighted the potential risk of cVDPV outbreaks in high-risk areas and/or communities in the WPR. Previous cVDPV outbreaks in the WPR have been rapidly and effectively controlled. However, future polio outbreak risks associated with cVDPVs must be reconsidered, and polio immunization and surveillance strategies should be updated accordingly.


Assuntos
Poliomielite , Vacina Antipólio Oral , Poliovirus , Surtos de Doenças , Saúde Global , Humanos , Poliomielite/epidemiologia , Poliomielite/prevenção & controle , Vacina Antipólio Oral/efeitos adversos , Organização Mundial da Saúde
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