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Bidirectional increase in permeability of nuclear envelope upon poliovirus infection and accompanying alterations of nuclear pores.

Poliovirus and some other picornaviruses trigger relocation of certain nuclear proteins into the cytoplasm. Here, by using a protein changing its fluorescence color with time and containing a nuclear localization signal (NLS), we demonstrate that the poliovirus-triggered relocation is largely due to the exit of presynthesized nuclear protein into the cytoplasm. The leakiness of the nuclear envelope was also documented by the inability of nuclei from digitonin-permeabilized, virus-infected (but not mock-infected) cells to retain an NLS-containing derivative of green fluorescent protein (GFP). T…

Coupled translation and replication of poliovirus RNA in vitro: synthesis of functional 3D polymerase and infectious virus.

Poliovirus RNA polymerase and infectious virus particles were synthesized by translation of virion RNA in vitro in HeLa S10 extracts. The in vitro translation reactions were optimized for the synthesis of the viral proteins found in infected cells and in particular the synthesis of the viral polymerase 3Dpol. There was a linear increase in the amount of labeled protein synthesized during the first 6 h of the reaction. The appearance of 3Dpol in the translation products was delayed because of the additional time required for the proteolytic processing of precursor proteins. 3Dpol was first obse…

Direct detection of wild poliovirus circulation by stool surveys of healthy children and analysis of community wastewater.

Cartagena, Colombia, was one of the last cities in the Americas known to have endemic poliomyelitis. After 3 cases were identified in 1991, two approaches for detecting continued silent transmission of wild polioviruses within a high-risk community were used: stool surveys of healthy children and virologic analysis of community sewage. Wild type 1 polioviruses were isolated from 8% of the children studied and from 21% of sewage samples. The proportions of wild polioviruses, vaccine-related polioviruses, and nonpolio enteric viruses were similar for both approaches. Wild poliovirus sequences we…

Different susceptibilities to attenuated poliovirus of cynomolgus monkeys from the Philippines and other Southeast Asian countries.

Susceptibilities to attenuated poliovirus of cynomolgus monkeys were assessed by the intraspinal inoculation method with the same single bulk lot as the reference for each of the three poliovirus types. The lesion-inducing virus dose in the spinal cord of 50% of monkeys inoculated (LID50) varied widely from 10(6.4) to lower than 10(2.5), the difference being as much as 10,000-fold, depending on the birth place of the monkey. The birth places of the monkeys used were traced and categorized into the following three districts; the peninsular region, Indonesia and the Philippines. The LID50 value …

Specific interactions of HeLa cell proteins with proposed translation domains of the poliovirus 5' noncoding region.

To determine which sequences or structures in the poliovirus 5' noncoding region (5'NCR) are involved in binding proteins used for internal ribosome binding and protein synthesis initiation, translation competition assays were performed in rabbit reticulocyte lysates in the presence and absence of HeLa cell extract. The results revealed two functional domains in the poliovirus 5'NCR. One, requiring nucleotides (nts) 457 to 626, binds proteins that are required for translation of all mRNAs and that are present in both reticulocyte lysates and HeLa cell extracts. Another, contained within nts 28…

Лечение постинфекцией с помощью антивирусной сыворотки приводит к выживанию нейронных клеток, продуктивно инфицированных вирулентным полиомиелитом.

Смерть клеток нейробластомы человека, страдающих от продуктивной инфекции вирулентным полиомиелитом, была предотвращена путем добавления антисеремии против вируса через несколько часов после начала инфекции; однако это лечение не помешало воспроизводству вируса. Несмотря на наличие вирусного антигена, клетки сохранили способность к разделению. При дальнейшем культивировании в отсутствие антисеремии клетки разработали специфический постинфекционный иммунитет или устойчивость к суперинфекции полиомиелитвирусом.

Совпадение в аннотации оригинала
The death of human neuroblastoma cells undergoing productive infection with virulent poliovirus was prevented by addition of antiserum against the virus a few hours after the onset of infection; this treatment, however, did not prevent reproduction of the virus. Despite the presence of the viral antigen, the cells retained the ability to divide. Upon further…

Antibody response of children immunized with poliovaccines: an evaluation using two strains of poliovirus type 1.

Neutralizing antibody response of children immunized with either OPV (3 doses), or IPV (2 doses) was evaluated against poliovirus type 1 Sabin vaccine strain and a local neurovirulent isolate. Both vaccines elicited significantly better antibody response against the vaccine strain than against the neurovirulent isolate. Moreover, approximately 35 per cent of sera contained very low levels of antibody against the virulent virus in spite of good antibody titre against the vaccine strain. The observed difference in antibody response to the wild and the vaccine strains was significant. The differe…

Immunogenicity, Safety and Immune Persistence of Sabin Strain Inactivated Poliovirus Vaccine: A Phase III Clinical Trial.

The phased transition from oral poliovirus vaccine (OPV) to full-course immunisation with inactivated poliovirus vaccine (IPV) is a critical strategy for the global eradication of poliomyelitis. A randomised, double-blind, multi-centre, active-controlled clinical trial was conducted among healthy infants in China to evaluate the immunogenicity and safety of the Sabin strain IPV (sIPV). A total of 1260 healthy 2-month-old infants who had not previously received poliovirus vaccination were randomly assigned to receive three doses of either the investigational vaccine (sIPV) or the control vaccin…

Poliovirus shedding after sequential immunization of Sabin-strain inactivated polio vaccines and oral attenuated polio vaccines.

The identification of poliovirus in stool samples post-Oral Poliovirus Vaccine (OPV) immunization is essential for implementing post-eradication monitoring of poliomyelitis. This research presents the inaugural assessment of the virus shedding rate and the genetic diversity of OPV shedding strains across different Inactivated Poliovirus Vaccine (IPV)-OPV sequential immunization schedules. Our findings revealed that the shedding rate of different serotypes in each sequential immunization groups peaked within 7 days following the initial administration of OPV, and then gradually decreased. Prior…

Assessing early detection ability through spatial arrangements in environmental surveillance for poliovirus: A simulation-based study.

Detecting the circulation of poliovirus in its early stages is paramount for swift public health action. While environmental surveillance (ES) is promising for enhancing early pathogen detection, the influence of spatial arrangement of ES sites on early detection remains unclear. Here, we aim to assess the early detection ability of ES by varying the number and location of ES sites using the simulation-based approach utilising geographic and demographic characteristics of South Africa as a case study of a non-endemic country. We developed a stochastic meta-population model among unimmunised ch…

Outbreaks of Circulating Vaccine-Derived Poliovirus in the World Health Organization Western Pacific Region, 2000-2021.

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 frequ…

Novel Network Method Major Minor Variation Clustering Enables Identification of Poliovirus Clusters with High-Resolution Linkages.

The Global Polio Eradication Initiative uses an outbreak response protocol that defines type 2 Sabin or Sabin-like virus as those with 0-5 nucleotides diverging from their parental strain in the complete VP1 genomic region. Sabin or Sabin-like viruses share highly similar genome sequences, regardless of their origin. Thus, it is challenging to distinguish viruses at a higher resolution to detect polio clusters or trace sources for local transmissions of viruses at an early stage. To identify type 2 Sabin or Sabin-like sources and improve our ability to map viral sources to campaigns during the

Use of guanidine thiocyanate-based nucleic acid extraction buffers to inactivate poliovirus in potentially infectious materials.

The efforts of the Global Poliovirus Eradication Initiative (GPEI) have brought about the near elimination of poliovirus worldwide. The World Health Organization has issued guidelines for the safe handling and containment of infectious materials (IM) and potentially infectious materials (PIM) following poliovirus eradication. Inactivation of poliovirus in IM and PIM is needed to prevent inadvertent re-introduction of polioviruses post-eradication. In this study, we investigated the use of guanidine thiocyanate-based nucleic acid extraction buffers from commercially available nucleic acid extra…

Antiviral Activity of Pocapavir in a Randomized, Blinded, Placebo-Controlled Human Oral Poliovirus Vaccine Challenge Model.

BACKGROUND: Immunodeficient individuals who excrete vaccine-derived polioviruses threaten polio eradication. Antivirals address this threat. METHODS: In a randomized, blinded, placebo-controlled study, adults were challenged with monovalent oral poliovirus type 1 vaccine (mOPV1) and subsequently treated with capsid inhibitor pocapavir or placebo. The time to virus negativity in stool was determined. RESULTS: A total of 144 participants were enrolled; 98% became infected upon OPV challenge. Pocapavir-treated subjects (n = 93) cleared virus a median duration of 10 days after challenge, compare…

Immune Serum From Sabin Inactivated Poliovirus Vaccine Immunization Neutralizes Multiple Individual Wild and Vaccine-Derived Polioviruses.

BACKGROUND: A Sabin strain-based inactivated poliomyelitis vaccine (Sabin-IPV) is the rational option for completely eradicating poliovirus transmission. The neutralizing capacity of Sabin-IPV immune serum to different strains of poliovirus is a key indicator of the clinical protective efficacy of this vaccine. METHODS: Sera collected from 500 infants enrolled in a randomized, blinded, positive control, phase 2 clinical trial were randomly divided into 5 groups: Groups A, B, and C received high, medium, and low doses, respectively, of Sabin-IPV, while groups D and E received trivalent oral po…

Regulatory Aspects of Sabin Type 2 Withdrawal From Trivalent Oral Poliovirus Vaccine: Process and Lessons Learned.

Withdrawal of type 2 oral poliovirus vaccine (OPV) in OPV-using countries required regulatory approval for use of inactivated poliovirus vaccine and bivalent OPV in routine immunization. Worldwide, a variety of mechanisms were used by member states, with some differences in approach observed between inactivated poliovirus vaccine and bivalent OPV. These included acceptance for use of World Health Organization (WHO) prequalified vaccines, registration and licensure pathways, participation in WHO-convened joint reviews of licensing dossiers, as well as pragmatic application of alternatively avai…