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Shutoff of RNA polymerase II transcription by poliovirus involves 3C protease-mediated cleavage of the TATA-binding protein at an alternative site: incomplete shutoff of transcription interferes with efficient viral replication.

The TATA-binding protein (TBP) plays a crucial role in cellular transcription catalyzed by all three DNA-dependent RNA polymerases. Previous studies have shown that TBP is targeted by the poliovirus (PV)-encoded protease 3C(pro) to bring about shutoff of cellular RNA polymerase II-mediated transcription in PV-infected cells. The processing of the majority of viral precursor proteins by 3C(pro) involves cleavages at glutamine-glycine (Q-G) sites. We present evidence that suggests that the transcriptional inactivation of TBP by 3C(pro) involves cleavage at the glutamine 104-serine 105 (Q104-S105…

Intestinal microbiota promote enteric virus replication and systemic pathogenesis.

Intestinal bacteria aid host health and limit bacterial pathogen colonization. However, the influence of bacteria on enteric viruses is largely unknown. We depleted the intestinal microbiota of mice with antibiotics before inoculation with poliovirus, an enteric virus. Antibiotic-treated mice were less susceptible to poliovirus disease and supported minimal viral replication in the intestine. Exposure to bacteria or their N-acetylglucosamine-containing surface polysaccharides, including lipopolysaccharide and peptidoglycan, enhanced poliovirus infectivity. We found that poliovirus binds lipopo…

Use of Inactivated Polio Vaccine Among U.S. Adults: Updated Recommendations of the Advisory Committee on Immunization Practices - United States, 2023.

Poliovirus can cause poliomyelitis and lifelong paralysis. Although wild poliovirus types 2 and 3 have been eradicated, wild poliovirus type 1 and vaccine-derived polioviruses are still circulating in multiple countries worldwide. In 2022, a case of paralytic polio caused by vaccine-derived poliovirus type 2 was identified in an unvaccinated young adult in New York. This case and subsequent detection of community transmission underscored the ongoing risk for importation of poliovirus into the United States and risk for poliomyelitis among unvaccinated persons. However, previous Advisory Commit…

Newcastle Disease Virus-Based Vectored Vaccine against Poliomyelitis.

The poliovirus eradication initiative has spawned global immunization infrastructure and dramatically decreased the prevalence of the disease, yet the original virus eradication goal has not been met. The suboptimal properties of the existing vaccines are among the major reasons why the program has repeatedly missed eradication deadlines. Oral live poliovirus vaccine (OPV), while affordable and effective, occasionally causes the disease in the primary recipients, and the attenuated viruses rapidly regain virulence and can cause poliomyelitis outbreaks. Inactivated poliovirus vaccine (IPV) is s…

The new polio eradication end game: rationale and supporting evidence.

Polio eradication requires the removal of all polioviruses from human populations, whether wild poliovirus or those emanating from the oral poliovirus vaccine (OPV). The Polio Eradication & Endgame Strategic Plan 2013-2018 provides a framework for interruption of wild poliovirus transmission in remaining endemic foci and lays out a plan for the new polio end game, which includes the withdrawal of Sabin strains, starting with type 2, and the introduction of inactivated poliovirus vaccine, for risk mitigation purposes. This report summarizes the rationale and evidence that supports the policy de…

Antipoliovirus activity and mechanism of action of 3-methylthio-5-phenyl-4-isothiazolecarbonitrile.

Our previous studies described the synthesis and the antiviral activity of 3,4,5-trisubstituted isothiazole derivatives that were found to be particularly effective against enteroviruses. Compound 3-methylthio-5-phenyl-4-isothiazolecarbonitrile (IS-2) exhibited an interesting anti-poliovirus activity with a high selectivity index. In the present study we investigated the mechanism of action of this compound. Studies on the time of IS-2 addition to poliovirus type 1 infected cells suggested that the compound may inhibit some early process of viral replication. In order to determine its mechanis…

Targeting the poliovirus receptor to activate T cells and induce myeloid-derived suppressor cells to differentiate to pro-inflammatory macrophages via the IFN-γ-p-STAT1-IRF8 axis in cancer therapy.

T cell immunoglobulin and ITIM domain (TIGIT) is one of the most important immune checkpoints expressed on lymphocytes, and poliovirus receptor (PVR, also CD155) serves as the most crucial ligand for TIGIT, harboring an important function in cancer cells and influencing the tumor microenvironment (TME). While it's well-established that TIGIT blockade could reverse immunosuppression, the question of whether direct inhibition of PVR yields comparable results remains to be fully elucidated. This study investigated the role of PVR within the TME on the LLC, CT26 and MC38 tumor models and found tha…

Immunogenicity of three doses of bivalent, trivalent, or type 1 monovalent oral poliovirus vaccines with a 2 week interval between doses in Bangladesh: an open-label, non-inferiority, randomised, controlled trial.

BACKGROUND: The provision of several doses of monovalent type 1 oral poliovirus vaccine (mOPV1) and bivalent OPV1 and 3 (bOPV) vaccines through campaigns is essential to stop the circulation of remaining wild polioviruses. Our study aimed to assess the shortening of intervals between campaigns with bOPV and mOPV1 and to assess the immunogenicity of bOPV in routine immunisation schedules. METHODS: We did an open-label, non-inferiority, five-arm, randomised controlled trial in Bangladesh. We recruited healthy infants aged 6 weeks at 42 immunisation clinics and randomly assigned them (with block…

Viral proteinase requirements for the nucleocytoplasmic relocalization of cellular splicing factor SRp20 during picornavirus infections.

Infection of mammalian cells by picornaviruses results in the nucleocytoplasmic redistribution of certain host cell proteins. These viruses interfere with import-export pathways, allowing for the cytoplasmic accumulation of nuclear proteins that are then available to function in viral processes. We recently described the cytoplasmic relocalization of cellular splicing factor SRp20 during poliovirus infection. SRp20 is an important internal ribosome entry site (IRES) trans-acting factor (ITAF) for poliovirus IRES-mediated translation; however, it is not known whether other picornaviruses utiliz…

Abortive and subclinical poliomyelitis in a family during the 1992 epidemic in The Netherlands.

We describe a case of abortive poliomyelitis due to poliovirus type 3 (PV3) in an unvaccinated woman and a subclinical poliovirus infection in her family during an epidemic in the Netherlands. The woman excreted the epidemic strain (PV3) for 7 weeks. Her two children received oral attenuated poliovirus vaccine and were subsequently found to excrete PV1 and PV2 vaccine strains in addition to the epidemic PV3 strain. Her husband, who had neutralizing antibodies to all three poliovirus types because of previous vaccination, initially excreted no virus; subsequently, however, the vaccine strain PV…

Containment of polioviruses after eradication and OPV cessation: characterizing risks to improve management.

The goal of the World Health Organization is to stop routine use of oral poliovirus vaccine shortly after interruption of wild poliovirus transmission. A key component of this goal is to minimize the risk of reintroduction by destruction of polioviruses except in an absolute minimum number of facilities that serve essential functions and implement effective containment. Effective containment begins with a complete facility risk assessment. This article focuses on characterizing the risks of exposure to polioviruses from the essential vaccine production, quality control, and international refer…

Progress toward poliomyelitis eradication--Bangladesh, 1995-1997.

As a member of the World Health Assembly, in 1988 Bangladesh adopted the goal of poliomyelitis eradication by 2000. To achieve this goal, Bangladesh has implemented the following strategies recommended by the World Health Organization (WHO): 1) achieving high routine coverage with at least three doses of oral poliovirus vaccine (OPV3) among infants aged <12 months; 2) conducting National Immunization Days (NIDs) to interrupt widespread circulation of poliovirus; 3) establishing sensitive systems for surveillance of polio cases and poliovirus that rely on acute flaccid paralysis (AFP) reporting…

Neurologic complications in oral polio vaccine recipients.

Between April 1982 and June 1983 four children 3 to 24 months of age were referred for evaluation of neurologic abnormalities found to be compatible with vaccine-related poliovirus infection, which had not been suspected by referring physicians. Patients were epidemiologically unrelated residents of Indiana, and none had prior symptoms suggestive of immunodeficiency. All had received poliovirus vaccine orally (first dose in three, fourth dose in one) and a diphtheria-tetanus-pertussis injection in the left anterior thigh within 30 days of symptoms. A vaccine-like strain of poliovirus was isola…

High level immunity against poliomyelitis in African and Asian refugees in southern Italy.

The aim of this study was to evaluate the level of poliomyelitis immunization in refugees residing in the Asylum Seeker Center in Bari. The study was carried out during 2008 and involved 573 refugees. An antibody titer >or=1:8 was found in 99.6% for poliovirus 1, in 99.8% for poliovirus 2, and in 99.5% for poliovirus 3.

Progress Toward Poliomyelitis Eradication - Worldwide, January 2021-March 2023.

Since the World Health Assembly established the Global Polio Eradication Initiative (GPEI) in 1988, two of the three wild poliovirus (WPV) serotypes (types 2 and 3) have been eradicated, and global WPV cases have decreased by more than 99.9%. Afghanistan and Pakistan remain the only countries where indigenous WPV type 1 (WPV1) transmission has not been interrupted. This report summarizes progress toward global polio eradication during January 1, 2021-March 31, 2023, and updates previous reports (1,2). In 2022, Afghanistan and Pakistan reported 22 WPV1 cases, compared with five in 2021; as of M…

Effectiveness of immunization against paralytic poliomyelitis in Nigeria.

BACKGROUND: The number of cases of paralytic poliomyelitis has declined in Nigeria since the introduction of newly licensed monovalent oral poliovirus vaccines and new techniques of vaccine delivery. Understanding the relative contribution of these vaccines and the improved coverage to the decline in incident cases is essential for future planning. METHODS: We estimated the field efficacies of monovalent type 1 oral poliovirus vaccine and trivalent oral poliovirus vaccine, using the reported number of doses received by people with poliomyelitis and by matched controls as identified in Nigeria…

Полиомиелит во время пандемии COVID-19 в Африке: усилия, проблемы и рекомендации.

Полиомиелит является главной причиной острого легкого паралича среди детей в возрасте до пяти лет, вызванного диким полиовирусом, без какого-либо другого медицинского лечения, кроме профилактики путем вакцинации. Проведение массовых кампаний по вакцинации от полиомиелита во всем мире привело к значительному сокращению числа случаев заболевания в мире и ограничило масштабы распространения этого заболевания. Вместе с тем появление полиовируса, полученного с помощью вакцин, в результате генетического обращения вспять в живой оральной вакцине против полиомиелита стало серьезным препятствием для гл

Совпадение в аннотации оригинала
Poliomyelitis is the leading infectious cause of acute flaccid paralysis among children under five years of age, caused by the Wild Poliovirus, with no medical cure other than prevention through vaccination. The advent of mass vaccination campaigns against polio disease worldwide has greatly decreased the number of global cases and limited the rate of transm…

Estimation of polio infection prevalence from environmental surveillance data.

A major obstacle to eradicating polio is that poliovirus from endemic countries can be reintroduced to polio-free countries. Environmental surveillance (ES) can detect poliovirus from sewage or wastewaters samples, even in the absence of patients with paralysis. ES is underused, in part because its sensitivity is unknown. We used two unique data sets collected during a natural experiment provided by the 2013 polio outbreak in Israel: ES data from different locations and records of supplemental immunization with the live vaccine. Data from the intersecting population between the two data sets (…

A new WHO International Reference Reagent for use in potency assays of inactivated poliomyelitis vaccine.

Assays of the potency of inactivated poliovirus vaccine require the use of an appropriate reference reagent. Preparation 91/574 was shown by international collaborative study to be suitable for determination of antigenic content and immunogenicity of inactivated poliovirus vaccines by in vitro and in vivo assays, respectively. The reagent is a trivalent blend of formaldehyde-inactivated monovalent pools of poliovirus type 1 (Mahoney) poliovirus type 2 (MEF-1) and poliovirus type 3 (Saukett). Studies by antigen-capture ELISA showed that the component monovalent pools contained high titres of D …

Immunity status to polioviruses among non-European union immigrants in Veneto Region (North-East Italy).

Widespread use of poliovirus vaccines has lead to a dramatic decline on the incidence of paralytic poliomyelitis in the Western Hemisphere. In Italy, the use of live attenuated vaccine (OPV) has lead to virtual eradication of poliomyelitis. However, wild poliovirus is still endemic in some less developed countries, and there is still a risk of importation of wild-virus poliomyelitis as result of immigration from these areas. Therefore, a serologic study of the immunologic status to poliovirus was carried out in 242 immigrants from less developed countries in the Veneto Region (North-East Italy…