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Sample records for sabin live poliovirus

  1. The Sabin live poliovirus vaccination trials in the USSR, 1959.

    PubMed Central

    Horstmann, D. M.

    1991-01-01

    Widespread use of the Sabin live attenuated poliovirus vaccine has had tremendous impact on the disease worldwide, virtually eliminating it from a number of countries, including the United States. Early proof of its safety and effectiveness was presented in 1959 by Russian investigators, who had staged massive trials in the USSR, involving millions of children. Their positive results were at first viewed in the United States and elsewhere with some skepticism, but the World Health Organization favored proceeding with large-scale trials, and responded to the claims made by Russian scientists by sending a representative to the USSR to review in detail the design and execution of the vaccine programs and the reliability of their results. The report that followed was a positive endorsement of the findings and contributed to the acceptance of the Sabin vaccine in the United States, where it has been the polio vaccine of choice since the mid-1960s. PMID:1814062

  2. Some results of the work on mass immunization in the Soviet Union with live poliovirus vaccine prepared from Sabin strains*

    PubMed Central

    Chumakov, M. P.; Voroshilova, M. K.; Drozdov, S. G.; Dzagurov, S. G.; Lashkevich, V. A.; Mironova, L. L.; Ralph, N. M.; Gagarina, A. V.; Ashmarina, E. E.; Shirman, G. A.; Fleer, G. P.; Tolskaya, E. A.; Sokolova, I. S.; Elbert, L. B.; Sinyak, K. M.

    1961-01-01

    In the course of campaigns for the mass immunization of large segments of the population of the Soviet Union with live poliovirus vaccine prepared in the USSR from attenuated Sabin strains, some 15 200 000 persons received oral vaccine in 1959 and over 77 478 800 persons (mainly between 2 months and 20 years old) in 1960. Approximately 95% of these were given the vaccine incorporated in dragées. The present paper gives data on the safety and immunological activity of the live vaccine, on virus carriage and transmission of the vaccine virus to contacts, and on virus interference. In a comparison between poliomyelitis incidence in 1960 in regions where mass live vaccine immunization had been carried out and the incidence in areas where inactivated Salk vaccine was used in 1958-60, it is shown that, while the Salk vaccine did not fundamentally influence the epidemic process, the Sabin live vaccine brought about a sharp reduction in incidence and prevented the usual summer-autumn rise in the number of poliomyelitis cases. It is concluded from the two years' experience in the mass use of live vaccine from Sabin strains that poliomyelitis epidemics can be prevented. PMID:13879389

  3. An infectious cDNA clone of the poliovirus Sabin strain could be used as a stable repository and inoculum for the oral polio live vaccine.

    PubMed

    Kohara, M; Abe, S; Kuge, S; Semler, B L; Komatsu, T; Arita, M; Itoh, H; Nomoto, A

    1986-05-01

    Viruses were recovered from HeLa S3 cells and African green monkey kidney (AGMK) cells transfected with an infectious cDNA clone of poliovirus vaccine Sabin 1 strain. The viruses recovered from the different DNA-transfected cells were tested for the biological characteristics of temperature sensitivity (rct marker), plaque size, and bicarbonate concentration dependency (d marker). The results revealed that the above properties were similar to those obtained from tests on the Sabin 1 vaccine reference strain. The recovered viruses and the vaccine reference virus were passaged in AGMK cells at an elevated temperature of 37.5 degrees, and the passaged isolates were tested for the rct marker. The virus recovered from AGMK cells had the most stable rct phenotype while the virus from HeLa S3 cells had a similar stability to that of the reference virus, suggesting that the virus from AGMK cells would be more suitable as a vaccine strain than the other two viruses. Furthermore, an infectious cDNA clone of high specific infectivity, constructed by introducing SV40 large T antigen into the plasmid, was used for production of high titers of virus after transfection. The results of in vitro biological tests on the recovered virus suggested that virus produced in the transfected AGMK cells also had the high quality that is desirable in vaccine stocks. Monkey neurovirulence tests performed with these recovered viruses revealed that the recovered viruses were weakly neurovirulent, similar to the vaccine reference virus. The infectious cDNA clone of the poliovirus vaccine strain could therefore be used to generate a possible inoculum of the oral polio live vaccine. Our findings strongly suggest that an infectious cDNA clone of poliovirus RNA may be used to preserve the constancy and quality of the present seed viruses of the Sabin 1 vaccine strain.

  4. Decay of Sabin inactivated poliovirus vaccine (IPV)-boosted poliovirus antibodies

    PubMed Central

    Resik, Sonia; Tejeda, Alina; Fonseca, Magile; Sein, Carolyn; Hung, Lai Heng; Martinez, Yenisleidys; Diaz, Manuel; Okayasu, Hiromasa; Sutter, Roland W.

    2015-01-01

    Introduction We conducted a follow-on study to a phase I randomized, controlled trial conducted in Cuba, 2012, to assess the persistence of poliovirus antibodies at 21–22 months following booster dose of Sabin-IPV compared to Salk-IPV in adults who had received multiple doses of oral poliovirus vaccine (OPV) during childhood. Methods In 2012, 60 healthy adult males aged 19–23 were randomized to receive one booster dose, of either Sabin-inactivated poliovirus vaccine (Sabin-IPV), adjuvanted Sabin-IPV (aSabin-IPV), or conventional Salk-IPV. In the original study, blood was collected at days 0 (before) and 28 (after vaccination), respectively. In this study, an additional blood sample was collected 21–22 months after vaccination, and tested for neutralizing antibodies to Sabin poliovirus types 1, 2 and 3. Results We collected sera from 59/60 (98.3%) subjects; 59/59 (100%) remained seropositive to all poliovirus types, 21–22 months after vaccination. The decay curves were very similar among the study groups. Between day 28 and 21–22 months, there was a reduction of ⩾87.4% in median antibody levels for all poliovirus types in all study groups, with no significant differences between the study groups. Conclusion The decay of poliovirus antibodies over a 21–22-month period was similar regardless of the type of booster vaccine used, suggesting the scientific data of Salk IPV long-term persistence and decay may be broadly applicable to Sabin IPV. PMID:27066157

  5. Development of inactivated poliovirus vaccine from Sabin strains: A progress report.

    PubMed

    Okayasu, Hiromasa; Sein, Carolyn; Hamidi, Ahd; Bakker, Wilfried A M; Sutter, Roland W

    2016-11-01

    The Global Polio Eradication Initiative (GPEI) has seen significant progress since it began in 1988, largely due to the worldwide use of oral poliovirus vaccine (OPV). In order to achieve polio eradication the global cessation of OPV is necessary because OPV contains live attenuated poliovirus, which in rare circumstances could re-gain wild poliovirus (WPV) characteristics with potential to establish transmission. The GPEI endgame strategy for the period 2013-2018 recommends the globally synchronised sequential cessation of the Sabin strains contained in the OPV, starting with type 2 Sabin. The withdrawal of Sabin type 2 took place in April 2016, with the introduction of at least one dose of inactivated poliovirus vaccine (IPV) as a risk mitigation strategy. The introduction of IPV into 126 countries since 2013 has required a rapid scale-up of IPV production by the two manufacturers supplying the global public sector market. This scale-up has been fraught with challenges, resulting in reductions of 40-50% of initial supply commitments. Consequently, 22 countries will not be supplied until 2018, and another 23 countries will experience serious stock-outs. In the last decade repeated calls-for-action were made to the global community to invigorate their vision and investment in developing "new poliovirus vaccines" including the development of IPV from less-virulent strains, such as Sabin-IPV (S-IPV). The conventional Salk-IPV production is limited to high-income industrialized-country manufacturers due to the containment requirements (i.e., high sanitation, low force-of-poliovirus-infection, and high population immunity). The use of Sabin strains in the production of S-IPV carries a lower biosafety risk, and was determined to be suitable for production in developing countries, expanding the manufacturing base and making IPV more affordable and accessible in the long term. Significant progress in the S-IPV has been made since 2006. S-IPV is now licensed as S-IPV in

  6. A Cluster of Paralytic Poliomyelitis Cases Due to Transmission of Slightly Diverged Sabin 2 Vaccine Poliovirus.

    PubMed

    Korotkova, Ekaterina A; Gmyl, Anatoly P; Yakovenko, Maria L; Ivanova, Olga E; Eremeeva, Tatyana P; Kozlovskaya, Liubov I; Shakaryan, Armen K; Lipskaya, Galina Y; Parshina, Irina L; Loginovskikh, Nataliya V; Morozova, Nadezhda S; Agol, Vadim I

    2016-07-01

    Four cases of acute flaccid paralysis caused by slightly evolved (Sabin-like) vaccine polioviruses of serotype 2 were registered in July to August 2010 in an orphanage of Biysk (Altai Region, Russia). The Biysk cluster of vaccine-associated paralytic poliomyelitis (VAPP) had several uncommon, if not unique, features. (i) Until this outbreak, Sabin-like viruses (in distinction to more markedly evolved vaccine-derived polioviruses [VDPVs]) were reported to cause only sporadic cases of VAPP. Consequently, VAPP cases were not considered to require outbreak-type responses. However, the Biysk outbreak completely blurred the borderline between Sabin-like viruses and VDPVs in epidemiological terms. (ii) The outbreak demonstrated a very high disease/infection ratio, apparently exceeding even that reported for wild polioviruses. The viral genome structures did not provide any substantial hints as to the underlying reason(s) for such pathogenicity. (iii) The replacement of intestinal poliovirus lineages by other Sabin-like lineages during short intervals after the disease onsets was observed in two patients. Again, the sequences of the respective genomes provided no clues to explain these events. (iv) The polioviruses isolated from the patients and their contacts demonstrated a striking heterogeneity as well as rapid and uneven evolution of the whole genomes and their parts, apparently due to extensive interpersonal contacts in a relatively small closed community, multiple bottlenecking, and recombination. Altogether, the results demonstrate several new aspects of pathogenicity, epidemiology, and evolution of vaccine-related polioviruses and underscore several serious gaps in understanding these problems. The oral poliovirus vaccine largely contributed to the nearly complete disappearance of poliovirus-caused poliomyelitis. Being generally safe, it can, in some cases, result in a paralytic disease. Two types of such outcomes are distinguished: those caused by slightly

  7. A Cluster of Paralytic Poliomyelitis Cases Due to Transmission of Slightly Diverged Sabin 2 Vaccine Poliovirus

    PubMed Central

    Korotkova, Ekaterina A.; Gmyl, Anatoly P.; Yakovenko, Maria L.; Ivanova, Olga E.; Eremeeva, Tatyana P.; Kozlovskaya, Liubov I.; Shakaryan, Armen K.; Lipskaya, Galina Y.; Parshina, Irina L.; Loginovskikh, Nataliya V.; Morozova, Nadezhda S.

    2016-01-01

    ABSTRACT Four cases of acute flaccid paralysis caused by slightly evolved (Sabin-like) vaccine polioviruses of serotype 2 were registered in July to August 2010 in an orphanage of Biysk (Altai Region, Russia). The Biysk cluster of vaccine-associated paralytic poliomyelitis (VAPP) had several uncommon, if not unique, features. (i) Until this outbreak, Sabin-like viruses (in distinction to more markedly evolved vaccine-derived polioviruses [VDPVs]) were reported to cause only sporadic cases of VAPP. Consequently, VAPP cases were not considered to require outbreak-type responses. However, the Biysk outbreak completely blurred the borderline between Sabin-like viruses and VDPVs in epidemiological terms. (ii) The outbreak demonstrated a very high disease/infection ratio, apparently exceeding even that reported for wild polioviruses. The viral genome structures did not provide any substantial hints as to the underlying reason(s) for such pathogenicity. (iii) The replacement of intestinal poliovirus lineages by other Sabin-like lineages during short intervals after the disease onsets was observed in two patients. Again, the sequences of the respective genomes provided no clues to explain these events. (iv) The polioviruses isolated from the patients and their contacts demonstrated a striking heterogeneity as well as rapid and uneven evolution of the whole genomes and their parts, apparently due to extensive interpersonal contacts in a relatively small closed community, multiple bottlenecking, and recombination. Altogether, the results demonstrate several new aspects of pathogenicity, epidemiology, and evolution of vaccine-related polioviruses and underscore several serious gaps in understanding these problems. IMPORTANCE The oral poliovirus vaccine largely contributed to the nearly complete disappearance of poliovirus-caused poliomyelitis. Being generally safe, it can, in some cases, result in a paralytic disease. Two types of such outcomes are distinguished: those caused

  8. CpG oligodeoxynucleotides are a potent adjuvant for an inactivated polio vaccine produced from Sabin strains of poliovirus.

    PubMed

    Yang, Chunting; Shi, Huiying; Zhou, Jun; Liang, Yanwen; Xu, Honglin

    2009-11-05

    Poliovirus transmission is controlled globally through world-wide use of a live attenuated oral polio vaccine (OPV). However, the imminence of global poliovirus eradication calls for a switch to the inactivated polio vaccine (IPV). Given the limited manufacturing capacity and high cost of IPV, this switch is unlikely in most developing and undeveloped countries. Adjuvantation is an effective strategy for antigen sparing. In this study, we evaluated the adjuvanticity of CpG oligodeoxynucleotides (CpG-ODN) for an experimental IPV produced from Sabin strains of poliovirus. Our results showed that CpG-ODN, alone or in combination with alum, can significantly enhance both the humoral and cellular immune responses to IPV in mice, and, consequently, the antigen dose could be reduced substantially. Therefore, our study suggests that the global use of IPV could be facilitated by using CpG-ODN or other feasible adjuvants.

  9. Isolation of sabin-like polioviruses from wastewater in a country using inactivated polio vaccine.

    PubMed

    Zurbriggen, Sebastian; Tobler, Kurt; Abril, Carlos; Diedrich, Sabine; Ackermann, Mathias; Pallansch, Mark A; Metzler, Alfred

    2008-09-01

    From 2001 to 2004, Switzerland switched from routine vaccination with oral polio vaccine (OPV) to inactivated polio vaccine (IPV), using both vaccines in the intervening period. Since IPV is less effective at inducing mucosal immunity than OPV, this change might allow imported poliovirus to circulate undetected more easily in an increasingly IPV-immunized population. Environmental monitoring is a recognized tool for identifying polioviruses in a community. To look for evidence of poliovirus circulation following cessation of OPV use, two sewage treatment plants located in the Zurich area were sampled from 2004 to 2006. Following virus isolation using either RD or L20B cells, enteroviruses and polioviruses were identified by reverse transcription-PCR. A total of 20 out of 174 wastewater samples were positive for 62 Sabin-like isolates. One isolate from each poliovirus-positive sample was analyzed in more detail. Sequencing the complete viral protein 1 (VP1) capsid coding region, as well as intratypic differentiation (ITD), identified 3 Sabin type 1, 13 Sabin type 2, and 4 Sabin type 3 strains. One serotype 1 strain showed a discordant result in the ITD. Three-quarters of the strains showed mutations within the 5' untranslated region and VP1, known to be associated with reversion to virulence. Moreover, three strains showed heterotypic recombination (S2/S1 and S3/S2/S3). The low number of synonymous mutations and the partial temperature sensitivity are not consistent with extended circulation of these Sabin virus strains. Nevertheless, the continuous introduction of polioviruses into the community emphasizes the necessity for uninterrupted child vaccination to maintain high herd immunity.

  10. Hematopoietic Cancer Cell Lines Can Support Replication of Sabin Poliovirus Type 1

    PubMed Central

    van Eikenhorst, Gerco; de Gruijl, Tanja D.; van der Pol, Leo A.; Bakker, Wilfried A. M.

    2015-01-01

    Viral vaccines can be produced in adherent or in suspension cells. The objective of this work was to screen human suspension cell lines for the capacity to support viral replication. As the first step, it was investigated whether poliovirus can replicate in such cell lines. Sabin poliovirus type 1 was serially passaged on five human cell lines, HL60, K562, KG1, THP-1, and U937. Sabin type 1 was capable of efficiently replicating in three cell lines (K562, KG1, and U937), yielding high viral titers after replication. Expression of CD155, the poliovirus receptor, did not explain susceptibility to replication, since all cell lines expressed CD155. Furthermore, we showed that passaged virus replicated more efficiently than parental virus in KG1 cells, yielding higher virus titers in the supernatant early after infection. Infection of cell lines at an MOI of 0.01 resulted in high viral titers in the supernatant at day 4. Infection of K562 with passaged Sabin type 1 in a bioreactor system yielded high viral titers in the supernatant. Altogether, these data suggest that K562, KG1, and U937 cell lines are useful for propagation of poliovirus. PMID:25815312

  11. [The role of Sabin inactivated poliovirus vaccine in the final phase of global polio eradication].

    PubMed

    Dong, S Z; Zhu, W B

    2016-12-06

    Global polio eradication has entered its final phase, but still faces enormous challenges. The Polio Eradication and Endgame Strategic Plan (2013-2018) set the target for making the world polio-free by 2018. Meanwhile, the World Heath Organization Global Action Plan (GAP Ⅲ) recommended that polioviruses be stored under strict conditions after eradication of the wild poliovirus. At least one dose of inactivated poliovirus vaccine (IPV) would be required for each newborn baby in the world to ensure successful completion of the final strategy and GAP Ⅲ. The Sabin IPV has a high production safety and low production cost, compared with the wild-virus IPV and, therefore, can play an important role in the final stage of global polio eradication.

  12. Differential induction of Toll-like receptors & type 1 interferons by Sabin attenuated & wild type 1 polioviruses in human neuronal cells

    PubMed Central

    Mohanty, Madhu C.; Deshpande, Jagadish M.

    2013-01-01

    Background & objectives: Polioviruses are the causative agent of paralytic poliomyelitis. Attenuated polioviruses (Sabin oral poliovirus vaccine strains) do not replicate efficiently in neurons as compared to the wild type polioviruses and therefore do not cause disease. This study was aimed to investigate the differential host immune response to wild type 1 poliovirus (wild PV) and Sabin attenuated type 1 poliovirus (Sabin PV) in cultured human neuronal cells. Methods: By using flow cytometry and real time PCR methods we examined host innate immune responses and compared the role of toll like receptors (TLRs) and cytoplasmic RNA helicases in cultured human neuronal cells (SK-N-SH) infected with Sabin PV and wild PV. Results: Human neuronal cells expressed very low levels of TLRs constitutively. Sabin PV infection induced significantly higher expression of TLR3, TLR7 and melanoma differentiation-associated protein-5 (MDA-5) m-RNA in neuronal cells at the beginning of infection (up to 4 h) as compared to wild PV. Further, Sabin PV also induced the expression of interferon α/β at early time point of infection. The induced expression of IFN α/β gene by Sabin PV in neuronal cells could be suppressed by inhibiting TLR7. Interpretation & conclusions: Neuronal cell innate immune response to Sabin and wild polioviruses differ significantly for TLR3, TLR7, MDA5 and type 1 interferons. Effects of TLR7 activation and interferon production and Sabin virus replication in neuronal cells need to be actively investigated in future studies. PMID:24056597

  13. A novel multiplex poliovirus binding inhibition assay applicable for large serosurveillance and vaccine studies, without the use of live poliovirus.

    PubMed

    Schepp, Rutger M; Berbers, Guy A M; Ferreira, José A; Reimerink, Johan H; van der Klis, Fiona R

    2017-03-01

    Large-scale serosurveillance or vaccine studies for poliovirus using the "gold standard" WHO neutralisation test (NT) are very laborious and time consuming. With the polio eradication at hand and with the removal of live attenuated Sabin strains from the oral poliovirus vaccine (OPV), starting with type 2 (as of April 2016), laboratories will need to conform to much more stringent laboratory biosafety regulations when handling live poliovirus strains. In this study, a poliovirus binding inhibition multiplex immunoassay (polio MIA) using inactivated poliovirus vaccine (IPV-Salk) was developed for simultaneous quantification of serum antibodies directed to all three poliovirus types. Our assay shows a good correlation with the NT and an excellent correlation with the ELISA-based binding inhibition assay (POBI). The assay is highly type-specific and reproducible. Additionally, serum sample throughput increases about fivefold relative to NT and POBI and the amount of serum needed is reduced by more than 90%. In conclusion, the polio MIA can be used as a safe and high throughput application, especially for large-scale surveillance and vaccine studies, reducing laboratory time and serum amounts needed. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  14. Relative sensitivity of three cell substrates to the Sabin poliovirus strains.

    PubMed

    Kado, G

    Poliovirus types 1, 2 and 3 (Sabin strains) were titrated using microtissue culture plates in three different cell substrates: Hep 2C, Vero and MRC-5 human diploid cells. Each type of poliovirus was titrated 60 times. The virus dilutions were inoculated in the three cell substrates and the titres (TCID50/ml) calculated by the Spearman-Kärber method. The results were analyzed by the U-test (Mann and Whitney procedure) in a Wang 600 computer. For poliovirus type 1 the differences in titres observed between Hep 2C and Vero cells were not statistically significant at p = 0.01, but the differences in titres between Hep 2C and MRC-5 human diploid cells and between Vero and MRC-5 cells were statistically highly significant (p = 0.001). For poliovirus types 2 and 3 the observed differences in titres were highly significant (p = 0.001) between Hep 2C and Vero cells, Hep 2C and MRC-5 and also between Vero and MRC-5 cells, with higher titres on Hep 2C cells. Accordingly with these results Hep 2C and Vero cells showed the same susceptibility to poliovirus type 1. In MCR-5 cells the average titre (G.M.T.) was 1 log10 below the average titres (G.M.T.) from Hep 2C or Vero cells. With poliovirus types 2 and 3 the higher titres were obtained on Hep 2C cells with significant differences to the titres observed in Vero and MRC-5 human diploid cells, which showed less susceptibility.

  15. Changes in population dynamics during long-term evolution of sabin type 1 poliovirus in an immunodeficient patient.

    PubMed

    Odoom, John K; Yunus, Zaira; Dunn, Glynis; Minor, Philip D; Martín, Javier

    2008-09-01

    The evolution of the Sabin strain of type 1 poliovirus in a hypogammaglobulinemia patient for a period of 649 days is described. Twelve poliovirus isolates from sequential stool samples encompassing days 21 to 649 after vaccination with Sabin 1 were characterized in terms of their antigenic properties, virulence in transgenic mice, sensitivity for growth at high temperatures, and differences in nucleotide sequence from the Sabin 1 strain. Poliovirus isolates from the immunodeficient patient evolved gradually toward non-temperature-sensitive and neurovirulent phenotypes, accumulating mutations at key nucleotide positions that correlated with the observed reversion to biological properties typical of wild polioviruses. Analysis of plaque-purified viruses from stool samples revealed complex genetic and evolutionary relationships between the poliovirus strains. The generation of various coevolving genetic lineages incorporating different mutations was observed at early stages of virus excretion. The main driving force for genetic diversity appeared to be the selection of mutations at attenuation sites, particularly in the 5' noncoding region and the VP1 BC loop. Recombination between virus strains from the two main lineages was observed between days 63 and 88. Genetic heterogeneity among plaque-purified viruses at each time point seemed to decrease with time, and only viruses belonging to a unique genotypic lineage were seen from day 105 after vaccination. The relevance of vaccine-derived poliovirus strains for disease surveillance and future polio immunization policies is discussed in the context of the Global Polio Eradication Initiative.

  16. Changes in Population Dynamics during Long-Term Evolution of Sabin Type 1 Poliovirus in an Immunodeficient Patient▿

    PubMed Central

    Odoom, John K.; Yunus, Zaira; Dunn, Glynis; Minor, Philip D.; Martín, Javier

    2008-01-01

    The evolution of the Sabin strain of type 1 poliovirus in a hypogammaglobulinemia patient for a period of 649 days is described. Twelve poliovirus isolates from sequential stool samples encompassing days 21 to 649 after vaccination with Sabin 1 were characterized in terms of their antigenic properties, virulence in transgenic mice, sensitivity for growth at high temperatures, and differences in nucleotide sequence from the Sabin 1 strain. Poliovirus isolates from the immunodeficient patient evolved gradually toward non-temperature-sensitive and neurovirulent phenotypes, accumulating mutations at key nucleotide positions that correlated with the observed reversion to biological properties typical of wild polioviruses. Analysis of plaque-purified viruses from stool samples revealed complex genetic and evolutionary relationships between the poliovirus strains. The generation of various coevolving genetic lineages incorporating different mutations was observed at early stages of virus excretion. The main driving force for genetic diversity appeared to be the selection of mutations at attenuation sites, particularly in the 5′ noncoding region and the VP1 BC loop. Recombination between virus strains from the two main lineages was observed between days 63 and 88. Genetic heterogeneity among plaque-purified viruses at each time point seemed to decrease with time, and only viruses belonging to a unique genotypic lineage were seen from day 105 after vaccination. The relevance of vaccine-derived poliovirus strains for disease surveillance and future polio immunization policies is discussed in the context of the Global Polio Eradication Initiative. PMID:18596089

  17. Microevolution of type 3 Sabin strain of poliovirus in cell cultures and its implications for oral poliovirus vaccine quality control.

    PubMed

    Rezapkin, G V; Norwood, L P; Taffs, R E; Dragunsky, E M; Levenbook, I S; Chumakov, K M

    1995-08-20

    Screening for sequence heterogeneities in Sabin Type 3 strains of attenuated poliovirus demonstrated mutations that consistently accumulate to significant levels following 10 passages in cultures of primary African green monkey kidney (AGMK) cells or continuous cultures of Vero cells. Fourteen newly identified mutations were quantified by mutant analysis by PCR and restriction enzyme cleavage in passages and in batches of commercial vaccines made in AGMK and Vero cells from the Sabin original (SO) seed virus and from a seed virus rederived by RNA plaque purification (RSO or "Pfizer" seed). Nine of the 14 mutations were reproducibly observed in more than one series of passages. Although 5 other mutations were observed in only one set of passages each, their content gradually increased to a high percentage, suggesting that all the mutations that we found accumulated consistently. SO-derived samples accumulated more mutations than did RSO-derived ones, and the number of mutations and the rates of their accumulation were higher in Vero than in AGMK cells. While the rates of accumulation of most mutations were higher when passaging was performed at 37 degrees, a U-->C transition at nucleotide 5832 occurred faster at 34 degrees, the temperature used for vaccine production. Analysis of Type 3 oral poliovirus vaccine (OPV) monopools made by six manufacturers found only 5 of these newly identified mutations in vaccine batches (nucleotides 3956, 4935, 5357, 5788, and 5832). Some of the mutations were found in trace amounts (less than 0.1%) while others were present at up to 1.8% levels. The pattern of these mutations was characteristic for the type of seed virus and the cell substrate but demonstrated no correlation with results of the monkey neurovirulence test. Therefore the only mutation occurring in Type 3 OPV which contributed to neurovirulence in monkeys was the previously described reversion at nucleotide 472. Quantitation of reversion at nucleotide 472 can be

  18. Microevolution of Sabin 1 strain in vitro and genetic stability of oral poliovirus vaccine.

    PubMed

    Rezapkin, G V; Chumakov, K M; Lu, Z; Ran, Y; Dragunsky, E M; Levenbook, I S

    1994-07-01

    Mutants consistently accumulating in Sabin 1 poliovirus during serial passaging in vitro were identified by sequence heterogeneity assay and quantitated using mutant analysis by PCR and restriction enzyme cleavage (MAPREC). Only four unstable genomic sites were identified in virus passaged 10 times in African green monkey kidney (AGMK) cells, and eight sites in virus passaged in Vero cells. Mutations accumulated both in untranslated regions of RNA (nucleotides 480, 525 and 7441) and in coding sequences, as missense (nucleotides 1449, 4944, and 6203) or silent (nucleotides 1123 and 1141) mutations. The most prominent selectable mutations were found at complementary nucleotides 480 and 525 of the 5'-untranslated region (5'-UTR) of the Sabin strain, changing the G:U pair in F-domain to either A:U or G:C variants. These two variants have been shown previously to have an increased neurovirulence in monkeys. The G:C variant accumulated during passage in Vero cells, while A:U variant accumulated in CV-1 cells. Virus passaged in AGMK cells accumulated both variants. Higher temperature (37 instead of 34 degrees) strongly favored selection of mutants in Vero cells, had a smaller effect on mutant accumulation in AGMK cells, and had no effect in CV-1 cells. Monopools of type 1 oral poliovirus vaccine (OPV) made by seven manufacturers were found to contain both 480-A and 525-C revertants at a combined level of 1.1-2.7%. Viral samples with increased amounts of these revertants had higher neurovirulence in monkeys. Our results suggest that quantitation of these reversions by MAPREC may be prognostic for results of the monkey neurovirulence test (MNVT) and can be used for monitoring type 1 OPV consistency.

  19. Safety and immunogenicity of inactivated poliovirus vaccine based on Sabin strains with and without aluminum hydroxide: a phase I trial in healthy adults.

    PubMed

    Verdijk, Pauline; Rots, Nynke Y; van Oijen, Monique G C T; Oberste, M Steven; Boog, Claire J; Okayasu, Hiromasa; Sutter, Roland W; Bakker, Wilfried A M

    2013-11-12

    An inactivated poliovirus vaccine (IPV) based on attenuated poliovirus strains (Sabin-1, -2 and -3) was developed for technology transfer to manufacturers in low- and middle income countries in the context of the Global Polio Eradication Initiative. Safety and immunogenicity of the Sabin-IPV was evaluated in a double-blind, randomized, controlled, phase I 'proof-of-concept' trial. Healthy male adults received a single intramuscular injection with Sabin-IPV, Sabin-IPV adjuvanted with aluminum hydroxide or conventional IPV. Virus-neutralizing titers against both Sabin and wild poliovirus strains were determined before and 28 days after vaccination. No vaccine-related serious adverse events were observed, and all local and systemic reactions were mild or moderate and transient. In all subjects, an increase in antibody titer for all types of poliovirus (both Sabin and wild strains) was observed 28 days after vaccination. Sabin-IPV and Sabin-IPV adjuvanted with aluminum hydroxide administered as a booster dose were equally immunogenic and safe as conventional IPV. EudraCTnr: 2010-024581-22, NCT01708720. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Comparative sensitivities of Sabin and Mahoney poliovirus type 1 prototype strains and two recent isolates to low concentrations of glutaraldehyde.

    PubMed Central

    Chambon, M; Jallat-Archimbaud, C; Bailly, J L; Gourgand, J M; Charbonne, F; Henquell, C; Fuchs, F; Peigue-Lafeuille, H

    1997-01-01

    Significant intratypic differences in the glutaraldehyde (GTA) sensitivity of echovirus isolates have been shown. While exploring ways to optimize the study of GTA sensitivity of enteroviruses, we also observed intratypic differences in poliovirus type 1 isolates collected in France. A suspension procedure was used for assessing the virucidal effect of GTA at low concentrations (< or = 0.10%) against purified viruses. Two recent isolates of poliovirus type 1 tested were first fully characterized by the PCR restriction fragment length polymorphism (RFLP) test. The RFLP pattern of clinical isolate 5617 was similar to that of poliovirus type 1 LS-c, 2ab (Sabin strain), confirming the vaccine origin of strain 5617. The RFLP pattern of strain 5915 recovered from sewage was different from that of the Mahoney strain, suggesting a genetic variation in this wild isolate. We then analyzed under the same controlled conditions the GTA sensitivities of both isolates and their respective prototype strains. The wild Mahoney and 5915 strains exhibited significantly lower sensitivities to GTA than did the vaccine Sabin and 5617 strains. The inactivation rates of clinical isolates 5617 and 5915 were very similar to those of their corresponding reference Sabin and Mahoney strains. Both the conformational structure of the capsid of each strain and the amino acid constitution of structural polypeptides could be involved in the variations observed. The relevance of our comparative sensitivity studies to standardization of virucidal tests is discussed. PMID:9251206

  1. Acute flaccid paralysis surveillance in bosnia and herzegovina: Recent isolation of two sabin like type 2 poliovirus.

    PubMed

    Fontana, Stefano; Buttinelli, Gabriele; Fiore, Stefano; Mulaomerovic, Mirsada; Aćimović, Jela; Amato, Concetta; Delogu, Roberto; Rezza, Giovanni; Stefanelli, Paola

    2017-09-01

    The WHO Regional Commission for the Certification of Poliomyelitis Eradication has recently indicated Bosnia and Herzegovina (B&H) as a high risk country for transmission, following importation, of wild poliovirus (WPV) or circulating vaccine-derived poliovirus (cVDPV). We analyzed data on Acute Flaccid Paralysis (AFP) surveillance between 2007 to 2016, and the trend of polio immunization coverage in B&H. The majority of AFP cases was recorded in 2016 suggesting an enhancement of the AFP surveillance activities. However, the decline in the immunization coverage, around 74%, and the isolation of two Sabin-like poliovirus type 2 strains, one of them close to a VDPV, require a particular attention in the area. Although B&H has successfully maintained its polio-free status since 2002 several challenges need to be addressed. © 2017 Wiley Periodicals, Inc.

  2. Nucleotide variation in Sabin type 3 poliovirus from an Albanian infant with agammaglobulinemia and vaccine associated poliomyelitis.

    PubMed

    Foiadelli, Thomas; Savasta, Salvatore; Battistone, Andrea; Kota, Majlinda; Passera, Carolina; Fiore, Stefano; Bino, Silvia; Amato, Concetta; Lozza, Alessandro; Marseglia, Gian Luigi; Fiore, Lucia

    2016-06-10

    Vaccine-associated paralytic poliomyelitis (VAPP) and immunodeficient long-term polio excretors constitute a significant public health burden and are a major concern for the WHO global polio eradication endgame. Poliovirus type 3 characterized as Sabin-like was isolated from a 5-month-old Albanian child with X-linked agammaglobulinemia and VAPP after oral polio vaccine administration. Diagnostic workup and treatment were performed in Italy. Poliovirus replicated in the gut for 7 months. The 5' non coding region (NCR), VP1, VP3 capsid proteins and the 3D polymerase genomic regions of sequential isolates were sequenced. Increasing accumulation of nucleotide mutations in the VP1 region was detected over time, reaching 1.0 % of genome variation with respect to the Sabin reference strain, which is the threshold that defines a vaccine-derived poliovirus (VDPV). We identified mutations in the 5'NCR and VP3 regions that are associated with reversion to neurovirulence. Despite this, all isolates were characterized as Sabin-like. Several amino acid mutations were identified in the VP1 region, probably involved in growth adaptation and viral persistence in the human gut. Intertypic recombination with Sabin type 2 polio in the 3D polymerase region, possibly associated with increased virus transmissibility, was found in all isolates. Gamma-globulin replacement therapy led to viral clearance and neurological improvement, preventing the occurrence of persistent immunodeficiency-related VDPV. This is the first case of VAPP in an immunodeficient child detected in Albania through the Acute Flaccid Paralysis surveillance system and the first investigated case of vaccine associated poliomyelitis in Italy since the introduction of an all-Salk schedule in 2002. We discuss over the biological and clinical implications in the context of the Global Polio Eradication Program and emphasize on the importance of the Acute Flaccid Paralysis surveillance.

  3. Stool screening of Syrian refugees and asylum seekers in Germany, 2013/2014: Identification of Sabin like polioviruses.

    PubMed

    Böttcher, Sindy; Neubauer, Katrin; Baillot, Armin; Rieder, Gabriele; Adam, Maja; Diedrich, Sabine

    2015-10-01

    Germany is a partner of the Global Polio Eradication Initiative. Assurance of polio free status is based on enterovirus surveillance, which focuses on patients with signs of acute flaccid paralysis or aseptic meningitis/encephalitis, representing the key symptoms of poliovirus infection. In response to the wild poliovirus outbreak in Syria 2013 and high number of refugees coming from Syria to Germany, stool samples from 629 Syrian refugees/asylum seekers aged <3 years were screened for wild poliovirus between November 2013 and April 2014. Ninety-three samples (14.8%) were positive in an enterovirus specific PCR. Of these, 12 contained Sabin-like polioviruses. The remaining 81 samples were characterized as non-polio enteroviruses representing several members of groups A-C as well as rhinovirus. Wild-type poliovirus was not detected via stool screening involving molecular and virological methods, indicating a very low risk for the importation by Syrian refugees and asylum seekers at that time. Copyright © 2015 Elsevier GmbH. All rights reserved.

  4. Sporadic Isolation of Sabin-Like Polioviruses and High-Level Detection of Non-Polio Enteroviruses during Sewage Surveillance in Seven Italian Cities, after Several Years of Inactivated Poliovirus Vaccination

    PubMed Central

    Battistone, A.; Buttinelli, G.; Fiore, S.; Amato, C.; Bonomo, P.; Patti, A. M.; Vulcano, A.; Barbi, M.; Binda, S.; Pellegrinelli, L.; Tanzi, M. L.; Affanni, P.; Castiglia, P.; Germinario, C.; Mercurio, P.; Cicala, A.; Triassi, M.; Pennino, F.

    2014-01-01

    Sewage surveillance in seven Italian cities between 2005 and 2008, after the introduction of inactivated poliovirus vaccination (IPV) in 2002, showed rare polioviruses, none that were wild-type or circulating vaccine-derived poliovirus (cVDPV), and many other enteroviruses among 1,392 samples analyzed. Two of five polioviruses (PV) detected were Sabin-like PV2 and three PV3, based on enzyme-linked immunosorbent assay (ELISA) and PCR results. Neurovirulence-related mutations were found in the 5′ noncoding region (5′NCR) of all strains and, for a PV2, also in VP1 region 143 (Ile > Thr). Intertypic recombination in the 3D region was detected in a second PV2 (Sabin 2/Sabin 1) and a PV3 (Sabin 3/Sabin 2). The low mutation rate in VP1 for all PVs suggests limited interhuman virus passages, consistent with efficient polio immunization in Italy. Nonetheless, these findings highlight the risk of wild or Sabin poliovirus reintroduction from abroad. Non-polio enteroviruses (NPEVs) were detected, 448 of which were coxsackievirus B (CVB) and 294 of which were echoviruses (Echo). Fifty-six NPEVs failing serological typing were characterized by sequencing the VP1 region (nucleotides [nt] 2628 to 2976). A total of 448 CVB and 294 Echo strains were identified; among those strains, CVB2, CVB5, and Echo 11 predominated. Environmental CVB5 and CVB2 strains from this study showed high sequence identity with GenBank global strains. The high similarity between environmental NPEVs and clinical strains from the same areas of Italy and the same periods indicates that environmental strains reflect the viruses circulating in the population and highlights the potential risk of inefficient wastewater treatments. This study confirmed that sewage surveillance can be more sensitive than acute flaccid paralysis (AFP) surveillance in monitoring silent poliovirus circulation in the population as well as the suitability of molecular approaches to enterovirus typing. PMID:24814793

  5. Sporadic isolation of sabin-like polioviruses and high-level detection of non-polio enteroviruses during sewage surveillance in seven Italian cities, after several years of inactivated poliovirus vaccination.

    PubMed

    Battistone, A; Buttinelli, G; Fiore, S; Amato, C; Bonomo, P; Patti, A M; Vulcano, A; Barbi, M; Binda, S; Pellegrinelli, L; Tanzi, M L; Affanni, P; Castiglia, P; Germinario, C; Mercurio, P; Cicala, A; Triassi, M; Pennino, F; Fiore, L

    2014-08-01

    Sewage surveillance in seven Italian cities between 2005 and 2008, after the introduction of inactivated poliovirus vaccination (IPV) in 2002, showed rare polioviruses, none that were wild-type or circulating vaccine-derived poliovirus (cVDPV), and many other enteroviruses among 1,392 samples analyzed. Two of five polioviruses (PV) detected were Sabin-like PV2 and three PV3, based on enzyme-linked immunosorbent assay (ELISA) and PCR results. Neurovirulence-related mutations were found in the 5'noncoding region (5'NCR) of all strains and, for a PV2, also in VP1 region 143 (Ile>Thr). Intertypic recombination in the 3D region was detected in a second PV2 (Sabin 2/Sabin 1) and a PV3 (Sabin 3/Sabin 2). The low mutation rate in VP1 for all PVs suggests limited interhuman virus passages, consistent with efficient polio immunization in Italy. Nonetheless, these findings highlight the risk of wild or Sabin poliovirus reintroduction from abroad. Non-polio enteroviruses (NPEVs) were detected, 448 of which were coxsackievirus B (CVB) and 294 of which were echoviruses (Echo). Fifty-six NPEVs failing serological typing were characterized by sequencing the VP1 region (nucleotides [nt] 2628 to 2976). A total of 448 CVB and 294 Echo strains were identified; among those strains, CVB2, CVB5, and Echo 11 predominated. Environmental CVB5 and CVB2 strains from this study showed high sequence identity with GenBank global strains. The high similarity between environmental NPEVs and clinical strains from the same areas of Italy and the same periods indicates that environmental strains reflect the viruses circulating in the population and highlights the potential risk of inefficient wastewater treatments. This study confirmed that sewage surveillance can be more sensitive than acute flaccid paralysis (AFP) surveillance in monitoring silent poliovirus circulation in the population as well as the suitability of molecular approaches to enterovirus typing.

  6. Development of oral CTL vaccine using a CTP-integrated Sabin 1 poliovirus-based vector system.

    PubMed

    Han, Seung-Soo; Lee, Jinjoo; Jung, Yideul; Kang, Myeong-Ho; Hong, Jung-Hyub; Cha, Min-Suk; Park, Yu-Jin; Lee, Ezra; Yoon, Cheol-Hee; Bae, Yong-Soo

    2015-09-11

    We developed a CTL vaccine vector by modification of the RPS-Vax system, a mucosal vaccine vector derived from a poliovirus Sabin 1 strain, and generated an oral CTL vaccine against HIV-1. A DNA fragment encoding a cytoplasmic transduction peptide (CTP) was integrated into the RPS-Vax system to generate RPS-CTP, a CTL vaccine vector. An HIV-1 p24 cDNA fragment was introduced into the RPS-CTP vector system and a recombinant poliovirus (rec-PV) named vRPS-CTP/p24 was produced. vRPS-CTP/p24 was genetically stable and efficiently induced Th1 immunity and p24-specific CTLs in immunized poliovirus receptor-transgenic (PVR-Tg) mice. In challenge experiments, PVR-Tg mice that were pre-immunized orally with vRPS-CTP/p24 were resistant to challenge with a lethal dose of p24-expressing recombinant vaccinia virus (rMVA-p24). These results suggested that the RPS-CTP vector system had potential for developing oral CTL vaccines against infectious diseases.

  7. Genetic stability and mutant selection in Sabin 2 strain of oral poliovirus vaccine grown under different cell culture conditions.

    PubMed

    Taffs, R E; Chumakov, K M; Rezapkin, G V; Lu, Z; Douthitt, M; Dragunsky, E M; Levenbook, I S

    1995-06-01

    Mutations that consistently accumulated in the attenuated Sabin 2 strain of poliovirus during propagation in cell cultures were identified by sequence heterogeneity assay and quantified by mutant analysis by PCR and restriction enzyme cleavage (MAPREC). Eight additional sites previously identified in stool isolates were also examined by MAPREC in the virus passages. The pattern of selectable mutations and the rate of their accumulation depended on the type and confluence of the cell culture and the temperature of virus growth. Five unstable genomic sites were identified in Sabin 2 virus passaged 10 times at 34 degrees in African green monkey kidney (AGMK) cells, with the mutations accumulating in the range 1 to 24%. Accumulation of these mutations did not appear to result in a loss of attenuated phenotype since the virus passaged under these conditions passed the monkey neurovirulence test (MNVT). The content of the 481-G revertant known to be related to neurovirulence in monkeys did not increase. Thus, our results suggest that upon growth of Sabin 2 virus in AGMK cells at 34 degrees, the key determinant(s) of attenuation remained stable, and the mutations that occurred did not affect monkey neurovirulence. In virus passaged 10 times at 37 degrees in AGMK cells, 4 unstable genomic sites were identified, in some of them accumulating up to 12% of the mutants. This virus sample severely failed the MNVT. Virus passaged in Vero cells at 34 and 37 degrees accumulated mutants at 7 and 14 genomic sites, respectively, including 481-G in both cases, with almost complete substitution of the original nucleotides at some of the sites. We tested 44 commercial monopools of Type 2 OPV and found out that all of them contained 481-G revertants in the range 0.4-1.1%. An increase in the 481-G revertants in passaged viruses to the level of 4% and above correlated with failure of these samples by the MNVT. Since the pattern of selectable mutations differed in viruses grown in the two

  8. Comparative in vivo efficiencies of hand-washing agents against hepatitis A virus (HM-175) and poliovirus type 1 (Sabin).

    PubMed Central

    Mbithi, J N; Springthorpe, V S; Sattar, S A

    1993-01-01

    The abilities of 10 hygienic hand-washing agents and tap water (containing approximately 0.5 ppm of free chlorine) to eliminate strain HM-175 of hepatitis A virus (HAV) and poliovirus (PV) type 1 (Sabin) were compared by using finger pad and whole-hand protocols with three adult volunteers. A mixture of the two viruses was prepared in a 10% suspension of feces, and 10 microliters of the mixture was placed on each finger pad. The inoculum was allowed to dry for 20 min, and the contaminated area was exposed to a hand-washing agent for 10 s, rinsed in tap water, and dried with a paper towel. In the whole-hand protocol, the hands were contaminated with 0.5 ml of the virus mixture, exposed for 10 s to a hand-washing agent, washed, and dried as described above. Tryptose phosphate broth was used to elute any virus remaining on the finger pads or hands. One part of the eluate was assayed directly for PV with FRhK-4 cells, while the other part was first treated with a PV-neutralizing serum and then assayed for HAV with the same cell line. The results are reported as mean percentages of reduction in PFU compared with the amount of infectious virus detectable after initial drying.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8250567

  9. Detection of negative and positive RNA strand of poliovirus Sabin 1 and echovirus E19 by a stem-loop reverse transcription PCR.

    PubMed

    Fikatas, A; Dimitriou, T G; Kyriakopoulou, Z; Moschonas, G D; Amoutzias, G D; Mossialos, D; Gartzonika, C; Levidiotou-Stefanou, S; Markoulatos, P

    2017-09-01

    In this report a strand specific RT-PCR was established for the detection of the replicative negative RNA strand of poliovirus sabin 1 (Sabin1) and Echovirus 19 (E19) strains. The key for the successful conduction of the assay was the use of a specific reverse transcription primer targeting the 5'-UTR of enteroviruses that consisted of a stem-loop structure at the 5'-end and an enteroviral-specific sequence at the 3'-end. The stem loop RT-PCR was found to be an accurate and sensitive method, detecting even 10(-2) CCID50 of poliovirus sabin 1 (Sabin1) and E19 strains 6 h postinfection (p.i.), while CPE appeared 3 days later. This assay was also validated in SiHa and Caski cell lines that are not used for the detection of enteroviruses. The negative RNA strand was detected 6 h and 12 h p.i. in SiHa and Caski cells, when these cell lines were inoculated with 10(5) and 1 CCID50 respectively, whereas CPE was observed 5 days p.i for SiHa cells and 8 days p.i for Caski cells and that only at 10(5) CCID50 . The results show that this approach may be used for replacing the time-consuming cell cultures in order to detect the active replication of enteroviruses. Enteroviruses are positive stranded RNA viruses that may cause severe diseases. The conventional method for detection of active viral replication involves virus isolation in sensitive cell cultures followed by titration and seroneutralization. In this report, we describe the use of a stem-loop secondary structured oligonucleotide in RT-PCR assay for the detection of the replicative negative strand of the positive-stranded RNA of poliovirus sabin 1 and E19 strains. This approach proved to be a useful tool that may be used for replacing the time-consuming cell culture assays in order to detect the active replication of enteroviruses. © 2017 The Society for Applied Microbiology.

  10. Rational design of genetically stable, live-attenuated poliovirus vaccines of all three serotypes: relevance to poliomyelitis eradication.

    PubMed

    Macadam, Andrew J; Ferguson, Geraldine; Stone, David M; Meredith, Janet; Knowlson, Sarah; Auda, Ghazi; Almond, Jeffrey W; Minor, Philip D

    2006-09-01

    The global eradication of poliomyelitis caused by wild-type virus is likely to be completed within the next few years, despite immense logistic and political difficulties, and may ultimately be followed by the cessation of vaccination. However, the existing live-attenuated vaccines have the potential to revert to virulence, causing occasional disease, and viruses can be shed by immunocompromised individuals for prolonged periods of time. Moreover, several outbreaks of poliomyelitis have been shown to be caused by viruses derived from the Sabin vaccine strains. The appearance of such strains depends on the prevailing circumstances but poses a severe obstacle to strategies for stopping vaccination. Vaccine strains that are incapable of reversion at a measurable rate would provide a possible solution. Here, we describe the constructions of strains of type 3 poliovirus that are stabilized by the introduction of four mutations in the 5' noncoding region compared to the present vaccine. The strains are genetically and phenotypically stable under conditions where the present vaccine loses the attenuating mutation in the 5' noncoding region completely. Type 1 and type 2 strains in which the entire 5' noncoding regions of Sabin 1 and Sabin 2 were replaced exactly with that of one of the type 3 strains were also constructed. The genetic stability of 5' noncoding regions of these viruses matched that of the type 3 strains, but significant phenotypic reversion occurred, illustrating the potential limitations of a rational approach to the genetic stabilization of live RNA virus vaccines.

  11. Inactivated polio vaccine development for technology transfer using attenuated Sabin poliovirus strains to shift from Salk-IPV to Sabin-IPV.

    PubMed

    Bakker, Wilfried A M; Thomassen, Yvonne E; van't Oever, Aart G; Westdijk, Janny; van Oijen, Monique G C T; Sundermann, Lars C; van't Veld, Peter; Sleeman, Eelco; van Nimwegen, Fred W; Hamidi, Ahd; Kersten, Gideon F A; van den Heuvel, Nico; Hendriks, Jan T; van der Pol, Leo A

    2011-09-22

    Industrial-scale inactivated polio vaccine (IPV) production dates back to the 1960s when at the Rijks Instituut voor de Volksgezondheid (RIV) in Bilthoven a process was developed based on micro-carrier technology and primary monkey kidney cells. This technology was freely shared with several pharmaceutical companies and institutes worldwide. In this contribution, the history of one of the first cell-culture based large-scale biological production processes is summarized. Also, recent developments and the anticipated upcoming shift from regular IPV to Sabin-IPV are presented. Responding to a call by the World Health Organization (WHO) for new polio vaccines, the development of Sabin-IPV was continued, after demonstrating proof of principle in the 1990s, at the Netherlands Vaccine Institute (NVI). Development of Sabin-IPV plays an important role in the WHO polio eradication strategy as biocontainment will be critical in the post-OPV cessation period. The use of attenuated Sabin strains instead of wild-type Salk polio strains will provide additional safety during vaccine production. Initially, the Sabin-IPV production process will be based on the scale-down model of the current, and well-established, Salk-IPV process. In parallel to clinical trial material production, process development, optimization and formulation research is being carried out to further optimize the process and reduce cost per dose. Also, results will be shown from large-scale (to prepare for future technology transfer) generation of Master- and Working virus seedlots, and clinical trial material (for phase I studies) production. Finally, the planned technology transfer to vaccine manufacturers in low and middle-income countries is discussed.

  12. Risks associated with the use of live-attenuated vaccine poliovirus strains and the strategies for control and eradication of paralytic poliomyelitis.

    PubMed

    Pliaka, Vaia; Kyriakopoulou, Zaharoula; Markoulatos, Panayotis

    2012-05-01

    The Global Polio Eradication Initiative was launched in 1988 with the aim to eliminate paralytic poliomyelitis. Two effective vaccines are available: inactivated polio vaccine (IPV) and oral polio vaccine (OPV). Since 1964, OPV has been used instead of IPV in most countries due to several economic and biological advantages. However, in rare cases, the live-attenuated Sabin strains of OPV revert to neurovirulence and cause vaccine-associated paralytic poliomyelitis in vaccinees or lead to emergence of vaccine-derived poliovirus strains. Attenuating mutations and recombination events have been associated with the reversion of vaccine strains to neurovirulence. The substitution of OPV with an improved new-generation IPV and the availability of new specific drugs against polioviruses are considered as future strategies for outbreak control and the eradication of paralytic poliomyelitis worldwide.

  13. A Sabin 3-Derived Poliovirus Recombinant Contained a Sequence Homologous with Indigenous Human Enterovirus Species C in the Viral Polymerase Coding Region†

    PubMed Central

    Arita, Minetaro; Zhu, Shuang-Li; Yoshida, Hiromu; Yoneyama, Tetsuo; Miyamura, Tatsuo; Shimizu, Hiroyuki

    2005-01-01

    Outbreaks of poliomyelitis caused by circulating vaccine-derived polioviruses (cVDPVs) have been reported in areas where indigenous wild polioviruses (PVs) were eliminated by vaccination. Most of these cVDPVs contained unidentified sequences in the nonstructural protein coding region which were considered to be derived from human enterovirus species C (HEV-C) by recombination. In this study, we report isolation of a Sabin 3-derived PV recombinant (Cambodia-02) from an acute flaccid paralysis (AFP) case in Cambodia in 2002. We attempted to identify the putative recombination counterpart of Cambodia-02 by sequence analysis of nonpolio enterovirus isolates from AFP cases in Cambodia from 1999 to 2003. Based on the previously estimated evolution rates of PVs, the recombination event resulting in Cambodia-02 was estimated to have occurred within 6 months after the administration of oral PV vaccine (99.3% nucleotide identity in VP1 region). The 2BC and the 3Dpol coding regions of Cambodia-02 were grouped into the genetic cluster of indigenous coxsackie A virus type 17 (CAV17) (the highest [87.1%] nucleotide identity) and the cluster of indigenous CAV13-CAV18 (the highest [94.9%] nucleotide identity) by the phylogenic analysis of the HEV-C isolates in 2002, respectively. CAV13-CAV18 and CAV17 were the dominant HEV-C serotypes in 2002 but not in 2001 and in 2003. We found a putative recombination between CAV13-CAV18 and CAV17 in the 3CDpro coding region of a CAV17 isolate. These results suggested that a part of the 3Dpol coding region of PV3(Cambodia-02) was derived from a HEV-C strain genetically related to indigenous CAV13-CAV18 strains in 2002 in Cambodia. PMID:16188967

  14. Immunization of newborn children with living oral trivalent poliovirus vaccine.

    PubMed

    CAMPILLO-SAINZ, C; ORNELAS HERNANDEZ, A; DE MUCHA MACIAS, J; NAVA, S E

    1962-09-01

    Campillo-Sainz, C. (Instituto Nacional de Virología de la S.S.A., México, D.F.), A. Ornelas Hernandez, J. de Mucha Macías, and S. E. Nava. Immunization of newborn children with living oral trivalent poliovirus vaccine. J. Bacteriol. 84:446-450. 1962.-The serological response to one dose of living oral trivalent polio-virus vaccine was compared in two groups of children, 49 vaccinated at birth and 44 vaccinated at the age of 4 months. Of those vaccinated at birth, 44 (90%) responded to the vaccine strains of type 1 and type 3 and 30 (61%) to the type 2 strain. Of those vaccinated at 4 months of age; 64% responded to type 1, 52% to type 2, and 82% to type 3. The difference between the responses of the two groups, which for type 1 is significant, may result from the interference of other enteric viruses in the 4-month-old children. A second dose of vaccine, administered to the children vaccinated at birth when they reached the age of 4 months, increased the over-all immunological response to 100% for types 1 and 3 and 96% for type 2, and showed that no immunological tolerance had been developed. The vaccine produced no undesirable effects in any of the children, and no paralytic poliomyelitis occurred among them. The observation of other investigators, that a high titer of maternal antibody inhibits immunological response to vaccination, was confirmed, but breast feeding apparently had no unfavorable effect on response.

  15. IMMUNIZATION OF NEWBORN CHILDREN WITH LIVING ORAL TRIVALENT POLIOVIRUS VACCINE

    PubMed Central

    Campillo-Sainz, C.; Hernandez, A. Ornelas; MacÍas, J. de Mucha; Nava, S. E.

    1962-01-01

    Campillo-Sainz, C. (Instituto Nacional de Virología de la S.S.A., México, D.F.), A. Ornelas Hernandez, J. de Mucha Macías, and S. E. Nava. Immunization of newborn children with living oral trivalent poliovirus vaccine. J. Bacteriol. 84:446–450. 1962.—The serological response to one dose of living oral trivalent polio-virus vaccine was compared in two groups of children, 49 vaccinated at birth and 44 vaccinated at the age of 4 months. Of those vaccinated at birth, 44 (90%) responded to the vaccine strains of type 1 and type 3 and 30 (61%) to the type 2 strain. Of those vaccinated at 4 months of age; 64% responded to type 1, 52% to type 2, and 82% to type 3. The difference between the responses of the two groups, which for type 1 is significant, may result from the interference of other enteric viruses in the 4-month-old children. A second dose of vaccine, administered to the children vaccinated at birth when they reached the age of 4 months, increased the over-all immunological response to 100% for types 1 and 3 and 96% for type 2, and showed that no immunological tolerance had been developed. The vaccine produced no undesirable effects in any of the children, and no paralytic poliomyelitis occurred among them. The observation of other investigators, that a high titer of maternal antibody inhibits immunological response to vaccination, was confirmed, but breast feeding apparently had no unfavorable effect on response. PMID:14018173

  16. Isoelectric point determination of live polioviruses by capillary isoelectric focusing with whole column imaging detection.

    PubMed

    Thomassen, Yvonne E; van Eikenhorst, Gerco; van der Pol, Leo A; Bakker, Wilfried A M

    2013-06-18

    Using a capillary isoelectric focusing-whole column imaging detection (CIEF-WCID) method, the isoelectric points (pI) of complete intact polioviruses were determined. The polioviruses that were analyzed are the commonly used viruses for the production of inactivated polio vaccines (IPV)-Mahoney (type 1), MEF (type 2), and Saukett (type 3)-as well as for attenuated oral polio vaccines (OPV) and Sabin types 1, 2, and 3. A method for analyzing biological hazardous components (biological safety level 2) was set up for the CIEF-WCID analyzer used. This method is based on closed circuits. The determined pI's were 6.2 for Mahoney, 6.7 for MEF-1, and 5.8 for Saukett. The pI's of Sabin types 1, 2, and 3 viruses were 7.4, 7.2, and 6.3, respectively. Resolution of the virus peaks was shown to be reproducible. Using this adjusted CIEF-WCID technique, the pI of biologically hazardous components like toxins or viruses can be determined, which is beneficial for the development of vaccine production methods among others.

  17. Oncolytic virotherapy for human bone and soft tissue sarcomas using live attenuated poliovirus.

    PubMed

    Atsumi, Satoru; Matsumine, Akihiko; Toyoda, Hidemi; Niimi, Rui; Iino, Takahiro; Nakamura, Tomoki; Matsubara, Takao; Asanuma, Kunihiro; Komada, Yoshihiro; Uchida, Atsumasa; Sudo, Akihiro

    2012-09-01

    The poliovirus receptor CD155, is essential for poliovirus to infect and induce death in neural cells. Recently, CD155 has been shown to be selectively expressed on certain types of tumor cells originating from the neural crest, including malignant glioma and neuroblastoma. However, the expression pattern of CD155 in soft tissue sarcoma has not been examined. Therefore, we first examined CD155 expression in sarcoma cell lines, and found the expression of both CD155 mRNA and protein in 12 soft and bone tissue sarcoma cell lines. Furthermore, we examined the effect of live attenuated poliovirus (LAPV) on 6 bone and soft tissue sarcoma cell lines in vitro, and found that LAPV induced apoptosis by activating caspases 7 and 3 in all of these cell lines. Furthermore, in BALB/c nu/nu mice xenotransplanted with HT1080 fibrosarcoma cells, administration of live attenuated poliovirus caused growth suppression of the tumors. These results suggest that oncolytic therapy using a LAPV may represent a new option for the treatment of bone and soft tissue sarcomas.

  18. Comparison of culture, single and multiplex real-time PCR for detection of Sabin poliovirus shedding in recently vaccinated Indian children.

    PubMed

    Giri, Sidhartha; Rajan, Anand K; Kumar, Nirmal; Dhanapal, Pavithra; Venkatesan, Jayalakshmi; Iturriza-Gomara, Miren; Taniuchi, Mami; John, Jacob; Abraham, Asha Mary; Kang, Gagandeep

    2017-02-18

    Although, culture is considered the gold standard for poliovirus detection from stool samples, real-time PCR has emerged as a faster and more sensitive alternative. Detection of poliovirus from the stool of recently vaccinated children by culture, single and multiplex real-time PCR was compared. Of the 80 samples tested, 55 (68.75%) were positive by culture compared to 61 (76.25%) and 60 (75%) samples by the single and one step multiplex real-time PCR assays respectively. Real-time PCR (singleplex and multiplex) is more sensitive than culture for poliovirus detection in stool, although the difference was not statistically significant.

  19. [History of development of the live poliomyelitis vaccine from Sabin attenuated strains in 1959 and idea of poliomyelitis eradication].

    PubMed

    Lashkevich, V A

    2013-01-01

    In 1958 Poliomyelitis Institute in Moscow and Institute of Experimental Medicine in St. Petersburg received from A. Sabin the attenuated strains of poliomyelitis virus. The characteristics of the strains were thoroughly studied by A. A. Smorodintsev and coworkers. They found that the virulence of the strains fluctuated slightly in 10 consecutive passages through the intestine of the non-immune children. A part of the Sabin material was used by A. A. Smorodintsev and M. P. Chumakov in the beginning of 1959 for immunizing approximately 40000 children in Estonia, Lithuania, and Latvia. Epidemic poliomyelitis rate in these republics decreased from approximately 1000 cases yearly before vaccination to less than 20 in the third quarter of 1959. This was a convincing proof of the efficacy and safety of the vaccine from the attenuated Sabin strains. In 1959, according to A. Sabin's recommendation, a technology of live vaccine production was developed at the Poliomyelitis Institute, and several experimental lots of vaccine were prepared. In the second part of 1959, 13.5 million children in USSR were immunized. The epidemic poliomyelitis rate decreased 3-5 times in different regions without paralytic cases, which could be attributed to the vaccination. These results were the final proof of high efficiency and safety of live poliomyelitis vaccine from the attenuated Sabin strains. Based on these results, A. Sabin and M. P. Chumakov suggested in 1960 the idea of poliomyelitis eradication using mass immunization of children with live vaccine. 72 million persons up to 20 years old were vaccinated in USSR in 1960 with a 5 times drop in the paralytic rate. 50-year-long use of live vaccine results in poliomyelitis eradication in almost all countries worldwide. More than 10 million children were rescued from the death and palsy. Poliomyelitis eradication in a few countries where it still exists depends not on medical services but is defined by the attitude of their leaders to fight

  20. Current status of poliovirus infections.

    PubMed

    Melnick, J L

    1996-07-01

    Two scientists who played leading roles in the conquest of poliomyelitis died recently. In 1954, Jonas Salk provided the first licensed polio vaccine, the formalin (and heat)-inactivated virus. Albert Sabin gave us the attenuated live virus vaccine, which was licensed in 1962. This paper takes the reader through the history of the disease, including its pathogenesis, epidemiology, vaccines, and future directions. The emphasis is on vaccines, for it seems that with proper vaccination the number of new cases is falling dramatically. It is hoped that by the year 2000, we will accomplish the goal of the World Health Organization of "a world without polio." Then, because there is no animal reservoir, we can seriously discuss when and how to eliminate the need for vaccination and ultimately destroy our stocks of poliovirus.

  1. Current status of poliovirus infections.

    PubMed Central

    Melnick, J L

    1996-01-01

    Two scientists who played leading roles in the conquest of poliomyelitis died recently. In 1954, Jonas Salk provided the first licensed polio vaccine, the formalin (and heat)-inactivated virus. Albert Sabin gave us the attenuated live virus vaccine, which was licensed in 1962. This paper takes the reader through the history of the disease, including its pathogenesis, epidemiology, vaccines, and future directions. The emphasis is on vaccines, for it seems that with proper vaccination the number of new cases is falling dramatically. It is hoped that by the year 2000, we will accomplish the goal of the World Health Organization of "a world without polio." Then, because there is no animal reservoir, we can seriously discuss when and how to eliminate the need for vaccination and ultimately destroy our stocks of poliovirus. PMID:8809461

  2. Sabin-to-Mahoney Transition Model of Quasispecies Replication

    SciTech Connect

    2009-05-31

    Qspp is an agent-based stochastic simulation model of the Poliovirus Sabin-to-Mahoney transition. This code simulates a cell-to-cell model of Poliovirus replication. The model tracks genotypes (virus genomes) as they are replicated in cells, and as the cells burst and release particles into the medium of a culture dish. An inoculum is then taken from the pool of virions and is used to inoculate cells on a new dish. This process repeats. The Sabin genotype comprises the initial inoculum. Nucleotide positions that match the Sabin1 (vaccine strain) and Mahoney (wild type) genotypes, as well as the neurovirulent phenotype (from the literature) are enumerated as constants.

  3. Circulating type 1 vaccine-derived poliovirus may evolve under the pressure of adenosine deaminases acting on RNA.

    PubMed

    Liu, Yanhan; Ma, Tengfei; Liu, Jianzhu; Zhao, Xiaona; Cheng, Ziqiang; Guo, Huijun; Xu, Ruixue; Wang, Shujing

    2015-01-01

    Poliovirus, the causative agent of poliomyelitis, is a human enterovirus and member of the Picornaviridae family. An effective live-attenuated poliovirus vaccine strain (Sabin 1) has been developed and has protected humans from polio. However, a few cases of vaccine virulence reversion have been documented in several countries. For instance, circulating type 1 vaccine-derived poliovirus is a highly pathogenic poliovirus that evolved from an avirulent strain, but the mechanism by which vaccine strains undergo reversion remains unclear. In this study, vaccine strains exhibited A to G/U to C and G to A/C to U hypermutations in the reversed evolution of Sabin 1. Furthermore, the mutation ratios of U to C and C to U were higher than those of other mutation types. Dinucleotide editing context was then analyzed. Results showed that A to G and U to C mutations exhibited preferences similar to adenosine deaminases acting on RNA (ADAR). Hence, ADARs may participate in poliovirus vaccine evolution.

  4. Poliovirus tropism and attenuation are determined after internal ribosome entry

    PubMed Central

    Kauder, Steven E.; Racaniello, Vincent R.

    2004-01-01

    Poliovirus replication is limited to a few organs, including the brain and spinal cord. This restricted tropism may be a consequence of organ-specific differences in translation initiation by the poliovirus internal ribosome entry site (IRES). A C-to-U mutation at base 472 in the IRES of the Sabin type 3 poliovirus vaccine strain, known to attenuate neurovirulence, may further restrict tropism by eliminating viral replication in the CNS. To determine the relationship between IRES-mediated translation and poliovirus tropism, recombinant human adenoviruses were used to express bicistronic mRNAs in murine organs. The IRESs of poliovirus, the cardiotropic coxsackievirus B3 (CVB3), and the hepatotropic hepatitis C virus (HCV) mediate translation in many organs, including those that do not support viral replication. A translation defect associated with the Sabin type 3 IRES was observed in all organs examined. Poliovirus type 1 and recombinant polioviruses dependent on the IRES of CVB3 or HCV replicate in the CNS of mice and cause paralysis. Although the type 3 Sabin strain is an effective vaccine, polioviruses with a U at base 472 of the IRES cause paralysis in newborn mice. Tropism of wild-type and vaccine strains of poliovirus is therefore determined after internal ribosome entry. PMID:15199409

  5. Factors affecting the efficacy of live poliovirus vaccine in warm climates

    PubMed Central

    Dömök, I.; Balayan, M. S.; Fayinka, O. A.; Škrtić, N.; Soneji, A. D.; Harland, P. S. E. G.

    1974-01-01

    A virologically controlled field trial was conducted with live monovalent type 1 poliovirus vaccine in children aged 3-30 months living in a rural area of Uganda, in an attempt to find out the reason for the poor efficacy of such vaccine often observed in countries with a warm climate. Groups of breast-fed and of artificially fed infants received the vaccine orally, either alone or mixed with horse serum prepared against partly purified human gamma-globulin. Irrespective of the diet, the “take rate”—measured by the rates of vaccine virus excretion and of antibody conversion—was found to be poor when the vaccine was given alone but satisfactory when it was given together with the horse antiserum. However, the extent and duration of vaccine virus multiplication in the intestinal tract proved to be limited and the mean antibody level elicited by the vaccination, irrespective of the schedule of vaccine administration, was low. These results, besides indicating that breast-feeding does not influence the efficacy of vaccination in the age groups studied, revealed the presence of an inhibitor in the alimentary tract. This inhibitor acts against the multiplication of vaccine virus, which may be blocked by antibodies in the horse antiserum for a limited period at the time of vaccination. Interference between the enteroviruses and the vaccine strain was also found to be responsible for decreasing the efficacy of vaccination, though its role was secondary to that of the inhibitor. Revaccination experiments showed that the effects of both inhibitor and interference may be overcome by repeated administration of the vaccine. PMID:4142936

  6. Different virucidal activities of hyperbranched quaternary ammonium coatings on poliovirus and influenza virus.

    PubMed

    Tuladhar, Era; de Koning, Martijn C; Fundeanu, Irina; Beumer, Rijkelt; Duizer, Erwin

    2012-04-01

    Virucidal activity of immobilized quaternary ammonium compounds (IQACs) coated onto glass and plastic surfaces was tested against enveloped influenza A (H1N1) virus and nonenveloped poliovirus Sabin1. The IQACs tested were virucidal against the influenza virus within 2 min, but no virucidal effect against poliovirus was found in 6 h.

  7. Long-term excretion of vaccine-derived poliovirus by a healthy child.

    PubMed

    Martín, Javier; Odoom, Kofi; Tuite, Gráinne; Dunn, Glynis; Hopewell, Nicola; Cooper, Gill; Fitzharris, Catherine; Butler, Karina; Hall, William W; Minor, Philip D

    2004-12-01

    A child was found to be excreting type 1 vaccine-derived poliovirus (VDPV) with a 1.1% sequence drift from Sabin type 1 vaccine strain in the VP1 coding region 6 months after he was immunized with oral live polio vaccine. Seventeen type 1 poliovirus isolates were recovered from stools taken from this child during the following 4 months. Contrary to expectation, the child was not deficient in humoral immunity and showed high levels of serum neutralization against poliovirus. Selected virus isolates were characterized in terms of their antigenic properties, virulence in transgenic mice, sensitivity for growth at high temperatures, and differences in nucleotide sequence from the Sabin type 1 strain. The VDPV isolates showed mutations at key nucleotide positions that correlated with the observed reversion to biological properties typical of wild polioviruses. A number of capsid mutations mapped at known antigenic sites leading to changes in the viral antigenic structure. Estimates of sequence evolution based on the accumulation of nucleotide changes in the VP1 coding region detected a "defective" molecular clock running at an apparent faster speed of 2.05% nucleotide changes per year versus 1% shown in previous studies. Remarkably, when compared to several type 1 VDPV strains of different origins, isolates from this child showed a much higher proportion of nonsynonymous versus synonymous nucleotide changes in the capsid coding region. This anomaly could explain the high VP1 sequence drift found and the ability of these virus strains to replicate in the gut for a longer period than expected.

  8. Long-Term Excretion of Vaccine-Derived Poliovirus by a Healthy Child

    PubMed Central

    Martín, Javier; Odoom, Kofi; Tuite, Gráinne; Dunn, Glynis; Hopewell, Nicola; Cooper, Gill; Fitzharris, Catherine; Butler, Karina; Hall, William W.; Minor, Philip D.

    2004-01-01

    A child was found to be excreting type 1 vaccine-derived poliovirus (VDPV) with a 1.1% sequence drift from Sabin type 1 vaccine strain in the VP1 coding region 6 months after he was immunized with oral live polio vaccine. Seventeen type 1 poliovirus isolates were recovered from stools taken from this child during the following 4 months. Contrary to expectation, the child was not deficient in humoral immunity and showed high levels of serum neutralization against poliovirus. Selected virus isolates were characterized in terms of their antigenic properties, virulence in transgenic mice, sensitivity for growth at high temperatures, and differences in nucleotide sequence from the Sabin type 1 strain. The VDPV isolates showed mutations at key nucleotide positions that correlated with the observed reversion to biological properties typical of wild polioviruses. A number of capsid mutations mapped at known antigenic sites leading to changes in the viral antigenic structure. Estimates of sequence evolution based on the accumulation of nucleotide changes in the VP1 coding region detected a “defective” molecular clock running at an apparent faster speed of 2.05% nucleotide changes per year versus 1% shown in previous studies. Remarkably, when compared to several type 1 VDPV strains of different origins, isolates from this child showed a much higher proportion of nonsynonymous versus synonymous nucleotide changes in the capsid coding region. This anomaly could explain the high VP1 sequence drift found and the ability of these virus strains to replicate in the gut for a longer period than expected. PMID:15564492

  9. Genomic Analysis of Vaccine-Derived Poliovirus Strains in Stool Specimens by Combination of Full-Length PCR and Oligonucleotide Microarray Hybridization

    PubMed Central

    Laassri, Majid; Dragunsky, Eugenia; Enterline, Joan; Eremeeva, Tatiana; Ivanova, Olga; Lottenbach, Kathleen; Belshe, Robert; Chumakov, Konstantin

    2005-01-01

    Sabin strains of poliovirus used in the manufacture of oral poliovirus vaccine (OPV) are prone to genetic variations that occur during growth in cell cultures and the organisms of vaccine recipients. Such derivative viruses often have increased neurovirulence and transmissibility, and in some cases they can reestablish chains of transmission in human populations. Monitoring for vaccine-derived polioviruses is an important part of the worldwide campaign to eradicate poliomyelitis. Analysis of vaccine-derived polioviruses requires, as a first step, their isolation in cell cultures, which takes significant time and may yield viral stocks that are not fully representative of the strains present in the original sample. Here we demonstrate that full-length viral cDNA can be PCR amplified directly from stool samples and immediately subjected to genomic analysis by oligonucleotide microarray hybridization and nucleotide sequencing. Most fecal samples from healthy children who received OPV were found to contain variants of Sabin vaccine viruses. Sequence changes in the 5′ untranslated region were common, as were changes in the VP1-coding region, including changes in a major antigenic site. Analysis of stool samples taken from cases of acute flaccid paralysis revealed the presence of mixtures of recombinant polioviruses, in addition to the emergence of new sequence variants. Avoiding the need for cell culture isolation dramatically shortened the time needed for identification and analysis of vaccine-derived polioviruses and could be useful for preliminary screening of clinical samples. The amplified full-length viral cDNA can be archived and used to recover live virus for further virological studies. PMID:15956413

  10. Plaque and growth characteristics of different polioviruses isolated from acute flaccid paralysis in Northern Nigeria.

    PubMed

    Sule, W F; Oyedele, O I; Osei-Kwasi, M; Odoom, J K; Adu, F D

    2008-03-01

    To determine some virulent trait-related properties of poliovirus isolates from children with acute flaccid paralysis following vaccination with oral polio vaccine (OPV). Six polioviruses earlier characterised into wild, vaccine-derived and OPV-like were studied using the plaque morphology and growth kinetics at supra-optimal temperature. Department of Virology, University of Ibadan, Nigeria. Polio isolates from six children who developed acute flaccid paralysis following vaccinations with various doses of OPV were used. All the children were located in the Northern part of the country where poliovirus is still circulating. The two vaccine-derived polioviruses acquired wild type characteristics. All the six poliovirus isolates developed different forms of plaques ranging from tiny, small and large. The plaque formed could however not be used to identify the different isolates. Growth of the different isolates at supra-optimal temperature showed that the three wild polioviruses grew to a higher titre when compared with the Sabin 2 control. The two vaccine derived isolates behaved like the wild poliovirus while the OPV-like virus acquired an intermediate characteristics between wild and sabin. The wild polioviruses represented in this study are among the last vestiges of the circulating polioviruses found in the world. It is possible that the observed biological properties of wild types 1 and 3 described in the study are typical of the West African polioviruses. These properties will provide useful previews to the final identification of some important clinical isolates especially type 1 which may grow rapidly in cell culture.

  11. Inactivated poliovirus type 2 vaccine delivered to rat skin via high density microprojection array elicits potent neutralising antibody responses

    PubMed Central

    Muller, David A.; Pearson, Frances E.; Fernando, Germain J.P.; Agyei-Yeboah, Christiana; Owens, Nick S.; Corrie, Simon R.; Crichton, Michael L.; Wei, Jonathan C.J.; Weldon, William C.; Oberste, M. Steven; Young, Paul R.; Kendall, Mark A. F.

    2016-01-01

    Polio eradication is progressing rapidly, and the live attenuated Sabin strains in the oral poliovirus vaccine (OPV) are being removed sequentially, starting with type 2 in April 2016. For risk mitigation, countries are introducing inactivated poliovirus vaccine (IPV) into routine vaccination programs. After April 2016, monovalent type 2 OPV will be available for type 2 outbreak control. Because the current IPV is not suitable for house-to-house vaccination campaigns (the intramuscular injections require health professionals), we developed a high-density microprojection array, the Nanopatch, delivered monovalent type 2 IPV (IPV2) vaccine to the skin. To assess the immunogenicity of the Nanopatch, we performed a dose-matched study in rats, comparing the immunogenicity of IPV2 delivered by intramuscular injection or Nanopatch immunisation. A single dose of 0.2 D-antigen units of IPV2 elicited protective levels of poliovirus antibodies in 100% of animals. However, animals receiving IPV2 by IM required at least 3 immunisations to reach the same neutralising antibody titres. This level of dose reduction (1/40th of a full dose) is unprecedented for poliovirus vaccine delivery. The ease of administration coupled with the dose reduction observed in this study points to the Nanopatch as a potential tool for facilitating inexpensive IPV for mass vaccination campaigns. PMID:26911254

  12. Inactivated poliovirus type 2 vaccine delivered to rat skin via high density microprojection array elicits potent neutralising antibody responses.

    PubMed

    Muller, David A; Pearson, Frances E; Fernando, Germain J P; Agyei-Yeboah, Christiana; Owens, Nick S; Corrie, Simon R; Crichton, Michael L; Wei, Jonathan C J; Weldon, William C; Oberste, M Steven; Young, Paul R; Kendall, Mark A F

    2016-02-25

    Polio eradication is progressing rapidly, and the live attenuated Sabin strains in the oral poliovirus vaccine (OPV) are being removed sequentially, starting with type 2 in April 2016. For risk mitigation, countries are introducing inactivated poliovirus vaccine (IPV) into routine vaccination programs. After April 2016, monovalent type 2 OPV will be available for type 2 outbreak control. Because the current IPV is not suitable for house-to-house vaccination campaigns (the intramuscular injections require health professionals), we developed a high-density microprojection array, the Nanopatch, delivered monovalent type 2 IPV (IPV2) vaccine to the skin. To assess the immunogenicity of the Nanopatch, we performed a dose-matched study in rats, comparing the immunogenicity of IPV2 delivered by intramuscular injection or Nanopatch immunisation. A single dose of 0.2 D-antigen units of IPV2 elicited protective levels of poliovirus antibodies in 100% of animals. However, animals receiving IPV2 by IM required at least 3 immunisations to reach the same neutralising antibody titres. This level of dose reduction (1/40th of a full dose) is unprecedented for poliovirus vaccine delivery. The ease of administration coupled with the dose reduction observed in this study points to the Nanopatch as a potential tool for facilitating inexpensive IPV for mass vaccination campaigns.

  13. Environmental surveillance of poliovirus in sewage water around the introduction period for inactivated polio vaccine in Japan.

    PubMed

    Nakamura, Tomofumi; Hamasaki, Mitsuhiro; Yoshitomi, Hideaki; Ishibashi, Tetsuya; Yoshiyama, Chiharu; Maeda, Eriko; Sera, Nobuyuki; Yoshida, Hiromu

    2015-03-01

    Environmental virus surveillance was conducted at two independent sewage plants from urban and rural areas in the northern prefecture of the Kyushu district, Japan, to trace polioviruses (PVs) within communities. Consequently, 83 PVs were isolated over a 34-month period from April 2010 to January 2013. The frequency of PV isolation at the urban plant was 1.5 times higher than that at the rural plant. Molecular sequence analysis of the viral VP1 gene identified all three serotypes among the PV isolates, with the most prevalent serotype being type 2 (46%). Nearly all poliovirus isolates exhibited more than one nucleotide mutation from the Sabin vaccine strains. During this study, inactivated poliovirus vaccine (IPV) was introduced for routine immunization on 1 September 2012, replacing the live oral poliovirus vaccine (OPV). Interestingly, the frequency of PV isolation from sewage waters declined before OPV cessation at both sites. Our study highlights the importance of environmental surveillance for the detection of the excretion of PVs from an OPV-immunized population in a highly sensitive manner, during the OPV-to-IPV transition period.

  14. Molecular Properties of Poliovirus Isolates: Nucleotide Sequence Analysis, Typing by PCR and Real-Time RT-PCR.

    PubMed

    Burns, Cara C; Kilpatrick, David R; Iber, Jane C; Chen, Qi; Kew, Olen M

    2016-01-01

    Virologic surveillance is essential to the success of the World Health Organization initiative to eradicate poliomyelitis. Molecular methods have been used to detect polioviruses in tissue culture isolates derived from stool samples obtained through surveillance for acute flaccid paralysis. This chapter describes the use of realtime PCR assays to identify and serotype polioviruses. In particular, a degenerate, inosine-containing, panpoliovirus (panPV) PCR primer set is used to distinguish polioviruses from NPEVs. The high degree of nucleotide sequence diversity among polioviruses presents a challenge to the systematic design of nucleic acid-based reagents. To accommodate the wide variability and rapid evolution of poliovirus genomes, degenerate codon positions on the template were matched to mixed-base or deoxyinosine residues on both the primers and the TaqMan™ probes. Additional assays distinguish between Sabin vaccine strains and non-Sabin strains. This chapter also describes the use of generic poliovirus specific primers, along with degenerate and inosine-containing primers, for routine VP1 sequencing of poliovirus isolates. These primers, along with nondegenerate serotype-specific Sabin primers, can also be used to sequence individual polioviruses in mixtures.

  15. Effects of arildone on the immunogenicity of formalin-inactivated polioviruses.

    PubMed

    Abe, S; Yamaki, A; Doi, Y; Yoshioka, I

    1987-02-01

    Concentrated and purified Sabin and virulent strains of poliovirus types 1, 2 and 3 were inactivated with formalin at 37 C. By addition of 5.4 microM arildone, an antiviral agent, to the virus suspension, the stability of D antigen increased in both Sabin and virulent strains of all types, especially in virulent type 1 Mahoney strain. The drug had neither any inhibitory nor enhancing effect on the formalin inactivation. When antibody response was compared in guinea pigs, Sabin strains inactivated in the absence of arildone were less immunogenic against homotypic virulent strains than inactivated vaccine prepared from virulent strains. On the other hand, Sabin strains inactivated in the presence of arildone were equally immunogenic. These results indicate that it is possible to prepare from Sabin strains a potent and safe inactivated vaccine having an immunogenicity comparable to that prepared from virulent strains.

  16. Transgenic mice carrying the human poliovirus receptor: new animal models for study of poliovirus neurovirulence.

    PubMed Central

    Horie, H; Koike, S; Kurata, T; Sato-Yoshida, Y; Ise, I; Ota, Y; Abe, S; Hioki, K; Kato, H; Taya, C

    1994-01-01

    Recombinant viruses between the virulent Mahoney and attenuated Sabin 1 strains of poliovirus type 1 were subjected to neurovirulence tests using a transgenic (Tg) mouse line, ICR-PVRTg1, that carried the human poliovirus receptor gene. The Tg mice were inoculated intracerebrally with these recombinant viruses and observed for clinical signs, histopathological lesions, and viral antigens as parameters of neurovirulence of the viruses. These parameters observed in the Tg mice were different for different inoculated viruses. Dose-dependent incidences of paralysis and of death were observed in the Tg mice inoculated with any viruses used. This indicates that values of 50% lethal dose are useful to score a wide range of neurovirulence of poliovirus. The neurovirulence of individual viruses estimated by the Tg mouse model had a strong correlation with those estimated by monkey model. Consequently, the mouse tests identified the neurovirulence determinants on the genome of poliovirus that had been identified by monkey tests. In addition, the mouse tests revealed new neurovirulence determinants, that is, different nucleotides between the two strains at positions 189 and 21 and/or 935 in the 5'-proximal 1,122 nucleotides. The Tg mice used in this study may be suitable for replacing monkeys for investigating poliovirus neurovirulence. Images PMID:8289371

  17. Genomic Characterization of Human and Environmental Polioviruses Isolated in Albania

    PubMed Central

    Divizia, Maurizio; Palombi, Leonardo; Buonomo, Ersilia; Donia, Domenica; Ruscio, Vito; Equestre, Michele; Leno, Luljeta; Panà, Augusto; Degener, Anna Marta

    1999-01-01

    Between April and December 1996, a serious outbreak of poliomyelitis occurred in Albania; almost 140 subjects were involved, and the episode presented an unusually high mortality rate (12%). During the outbreak, water samples from the Lana River in Tirana, Albania, and stool samples from two cases of paralytic poliomyelitis were collected and analyzed for the presence of polioviruses. Six polioviruses were isolated from the environmental and human samples, according to standard methods. All the samples were characterized by partial genomic sequencing of 330 bases across the 5′ untranslated region (5′-UTR) (nucleotide positions 200 to 530) and of 300 bases across the VP1 region (nucleotide positions 2474 to 2774). Comparison of these sequences with those present in data banks permitted the identification of environmental isolates Lana A and Lana B as, respectively, a Sabin-like type 2 poliovirus and an intertypic recombinant poliovirus (Sabin-like type 2/wild type 1), both bearing a G instead of an A at nucleotide position 481. The two other environmental polioviruses were similar to the isolates from the paralytic cases. They were characterized by a peculiar 5′-UTR and by a VP1 region showing 98% homology with the Albanian epidemic type 1 isolates reported by other authors. This study confirms the environmental circulation in Albania of recombinant poliovirus strains, likely sustained by a massive vaccination effort and by the presence in the environment of a type 1 poliovirus, as isolated from the Lana River in Tirana about 2 months before the first case of symptomatic acute flaccid paralysis was reported in this town. PMID:10427045

  18. Serological survey on immunity status against polioviruses in children and adolescents living in a border region, Apulia (Southern Italy).

    PubMed

    Tafuri, Silvio; Prato, Rosa; Martinelli, Domenico; Calvario, Agata; Bozzi, Anna; Labianca, Michele; Patti, Annamaria; Lopalco, Pietro Luigi; Germinario, Cinzia

    2008-10-30

    In 1988 the World Health Assembly adopted the goal to eradicate poliomyelitis by routine immunization using Oral Polio Vaccine (OPV). On 21 June 2002 the WHO European Region was declared polio-free. In 2008 poliomyelitis is still endemic in 4 countries (Nigeria, India, Pakistan, and Afghanistan), where 1201 new cases were registered in 2007; 107 sporadic cases were also notified in countries where poliovirus is not endemic. The aim of this work was to verify the level of antipoliomyelitis immunity status in children and adolescents in the Apulia region (south of Italy), which may be considered a border region due to its position. 704 blood specimens from a convenience sample were collected in six laboratories. The age of subjects enrolled was 0-15 years. The immunity against poliomyelitis was evaluated by neutralizing antibody titration in tissue culture microplates. Seropositivity (neutralising antibodies titre > or = 8) for polioviruses 1, 2 and 3 was detected in 100%, 99.8% and 99.4% of collected sera. Antibody titres were not lower in subjects who received either four doses of inactivated polio vaccine (IPV) or a sequential schedule consisting of two doses of IPV and two of oral polio vaccine than in subjects who received four doses of OPV. These results confirmed current data of vaccine coverage for poliomyelitis: during the last ten years in Apulia, the coverage in 24 months old children was more than 90%. The high level of immunization found confirms the effectiveness both of the sequential schedule IPV-OPV and of the schedule all-IPV. Apulia region has to face daily arrivals of refugees and remains subject to the risk of the importation of poliovirus from endemic areas. Surveys aimed at determining anti-polio immunity in subpopulations as well as in the general population should be carried out.

  19. Registration of 'Sabine' Dallisgrass

    USDA-ARS?s Scientific Manuscript database

    'Sabine' dallisgrass (Paspalum dilatatum Poir.) (Reg. No. CV-2; PI 655527) was released by the USDA-Agricultural Research Service, Louisiana State University Agricultural Center, and Texas AgriLife Research on 2 September 2008. This cultivar is phenotypically and cytologically different from common...

  20. Detection of vaccine-derived polioviruses in Mexico using environmental surveillance.

    PubMed

    Esteves-Jaramillo, Alejandra; Estívariz, Concepción F; Peñaranda, Silvia; Richardson, Vesta L; Reyna, Jesús; Coronel, Diana L; Carrión, Veronica; Landaverde, Jose M; Wassilak, Steven G F; Pérez-Sánchez, Elda E; López-Martínez, Irma; Burns, Cara C; Pallansch, Mark A

    2014-11-01

    Early detection and control of vaccine-derived poliovirus (VDPV) emergences are essential to secure the gains of polio eradication. Serial sewage samples were collected in 4 towns of Mexico before, throughout, and after the May 2010 oral poliovirus vaccine (OPV) mass immunization campaign. Isolation and molecular analysis of polioviruses from sewage specimens monitored the duration of vaccine-related strains in the environment and emergence of vaccine-derived polioviruses in a population partially immunized with inactivated poliovirus vaccine (IPV). Sabin strains were identified up to 5-8 weeks after the campaign in all towns; in Aguascalientes, 1 Sabin 3 was isolated 16 weeks after the campaign, following 7 weeks with no Sabin strains detected. In Tuxtla Gutiérrez, type 2 VDPV was isolated from 4 samples collected before and during the campaign, and type 1 VDPV from 1 sample collected 19 weeks afterward. During 2009-2010, coverage in 4 OPV campaigns conducted averaged only 57% and surveillance for acute flaccid paralysis (AFP) was suboptimal (AFP rate<1 per 100,000 population<15 years of age) in Tuxtla Gutierrez. VDPVs may emerge and spread in settings with inadequate coverage with IPV/OPV vaccination. Environmental surveillance can facilitate early detection in these settings. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  1. Immunity status of adults and children against poliomyelitis virus type 1 strains CHAT and Sabin (LSc-2ab) in Germany

    PubMed Central

    2010-01-01

    Background In October 2007, the working group CEN/TC 216 of the European Committee for standardisation suggested that the Sabin oral poliovirus vaccine type 1 strain (LSc-2ab) presently used for virucidal tests should be replaced by another attenuated vaccine poliovirus type 1 strain, CHAT. Both strains were historically used as oral vaccines, but the Sabin type 1 strain was acknowledged to be more attenuated. In Germany, vaccination against poliomyelitis was introduced in 1962 using the oral polio vaccine (OPV) containing Sabin strain LSc-2ab. The vaccination schedule was changed from OPV to an inactivated polio vaccine (IPV) containing wild polio virus type 1 strain Mahoney in 1998. In the present study, we assessed potential differences in neutralising antibody titres to Sabin and CHAT in persons with a history of either OPV, IPV, or OPV with IPV booster. Methods Neutralisation poliovirus antibodies against CHAT and Sabin 1 were measured in sera of 41 adults vaccinated with OPV. Additionally, sera from 28 children less than 10 years of age and immunised with IPV only were analysed. The neutralisation assay against poliovirus was performed according to WHO guidelines. Results The neutralisation activity against CHAT in adults with OPV vaccination history was significantly lower than against Sabin poliovirus type 1 strains (Wilcoxon signed-rank test P < 0.025). In eight sera, the antibody titres measured against CHAT were less than 8, although the titre against Sabin 1 varied between 8 and 64. Following IPV booster, anti-CHAT antibodies increased rapidly in sera of CHAT-negative adults with OPV history. Sera from children with IPV history neutralised CHAT and Sabin 1 strains equally. Conclusion The lack of neutralising antibodies against the CHAT strain in persons vaccinated with OPV might be associated with an increased risk of reinfection with the CHAT polio virus type 1, and this implies a putative risk of transmission of the virus to polio-free communities. We

  2. Identification of vaccine-related polioviruses by hybridization with specific RNA probes.

    PubMed Central

    De, L; Nottay, B; Yang, C F; Holloway, B P; Pallansch, M; Kew, O

    1995-01-01

    We developed RNA probes for the identification of poliovirus isolates by blot hybridization. Two sets of vaccine strain-specific probes were prepared. They complemented variable genomic domains within (i) the 5'-untranslated region and (ii) the amino-terminal codons of VP1. An enterovirus group probe (EV/5UT) matching highly conserved 5'-untranslated region sequences was used to estimate the quantities of poliovirus (or enterovirus) RNA in the samples. Poliovirus sequences amplified from Sabin strain virion RNA templates by PCR were inserted into the pUC18 plasmid vector. The antisense PCR primer for each probe set contained sequences encoding a T7 promoter. Hybrids were detected by a sensitive nonisotopic method. RNA probes were labeled by incorporation of digoxigenin-uridylate into the transcripts. The binding of probe to immobilized poliovirus RNAs was visualized by hydrolysis of the chemiluminescent substrate 4-methoxy-4-(3-phosphate-phenyl)-spiro-(1,2-dioxetane-3,2'-adamant ane) catalyzed by alkaline phosphatase conjugated to anti-digoxigenin (Fab) fragments. The specificities of the probes were evaluated with a panel of poliovirus isolates that had previously been characterized by sequence analysis. The RNAs of vaccine-related isolates hybridized with the appropriate probe sets. Wild polioviruses representing a broad spectrum of contemporary genotypes were recognized by the inabilities of their genomes to form stable hybrids with the Sabin strain-specific probes. PMID:7751358

  3. Three cases of paralytic poliomyelitis associated with type 3 vaccine poliovirus strains in Bulgaria.

    PubMed

    Korsun, Neli; Kojouharova, Mira; Vladimirova, Nadezhda; Fiore, Lucia; Litvinenko, Ivan; Buttinelli, Gabriele; Fiore, Stefano; Voynova-Georgieva, Violeta; Mladenova, Zornitsa; Georgieva, Daniela

    2009-09-01

    Oral poliovirus vaccine (OPV) can cause, in extremely rare cases vaccine-associated paralytic poliomyelitis in recipients, or contacts of vaccinees. Three cases of vaccine-associated paralytic poliomyelitis (two contacts and one recipient) occurred in the Bourgas region of Bulgaria in the spring of 2006. The first two cases, notified as acute flaccid paralysis, were 55 days old unvaccinated twin brothers, having been in contact with vaccinees. The third case concerned a 4-month-old infant who had received the first OPV dose 37 days prior to the onset of illness. Complete clinical, epidemiological, virological, serological and molecular investigations of the children with paralysis and their contacts were undertaken. In all the three cases type 3 polioviruses were isolated from fecal samples and characterized as Sabin-like poliovirus strains. Type 3 polioviruses isolated from the twin brothers demonstrated by sequence analysis U-to-C back mutation at nt 472 of the 5' UTR, known to correlate with neurovirulence, and mutation in the VP1 region. Type 3 poliovirus isolated from the third child demonstrated in the 3D sequenced region a recombination with Sabin type 1 poliovirus. In the latter region, three silent mutations and one, resulting in amino acid substitution, were also observed. The clinical, epidemiological and virological data and the neurological sequelae observed 60 days following the onset of paralysis, confirmed the diagnosis of vaccine-associated paralytic poliomyelitis in all the three patients.

  4. Poliovirus and other enteroviruses in children infected with intestinal parasites in Nigeria.

    PubMed

    Adekolujo, Daniel R; Olayinka, Suraj O; Adeniji, Johnson A; Oyeyemi, Oyetunde T; Odaibo, Alexander B

    2015-10-29

    Poliovirus, an enterovirus, still persists in Nigeria despite the global efforts tailored towards its eradication. This study aimed to assess the impacts of poliovirus and other enteroviruses on the susceptibility of individuals to intestinal parasite infections. A cross-sectional study on the prevalence of intestinal parasites was conducted on two-sample stool specimens of 717 Nigerian children (between 1 and 19 years of age) whose poliovirus/other enteroviruses infection status had been determined. The overall prevalence of Sabin poliovirus and other related enteroviruses infections were 6.6% and 13.8%, respectively. The prevalence of Ascaris lumbricoides was significantly higher than that of other intestinal parasites (p < 0.05), with children in the 0-4 year age group being the most predisposed age group to intestinal parasitic infection (OR = 11.7, CI = 9.2-15.0). While the prevalence of all species of parasites except S. mansoni showed no significant variations in children with Sabin poliovirus (p > 0.05), the prevalence of hookworms and Taenia spp. was significantly higher in children with other enteroviral infections (p < 0.05). The high risk of children of acquiring enteroviral infection through some intestinal parasites is an indication of possible association of the parasites in a more poliovirus-endemic population. A combined intervention approach for the two infections is advocated.

  5. 78 FR 35625 - Sabine Pass Liquefaction Expansion, LLC; Sabine Pass Liquefaction, LLC; Sabine Pass LNG, L.P...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-13

    ..., LLC; Sabine Pass LNG, L.P.; Cheniere Creole Trail Pipeline, L.P.: Notice of Intent To Prepare an... Sabine Pass Liquefaction Expansion, LLC; Sabine Pass Liquefaction, LLC; and Sabine Pass LNG, L.P... metric tonnes of liquefied natural gas (LNG) per annum (mtpa) via LNG carriers. Trains 5 and 6...

  6. 78 FR 25432 - Sabine Pass LNG, L.P., Sabine Pass Liquefaction, LLC; Notice of Availability of the Environmental...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-01

    ... Energy Regulatory Commission Sabine Pass LNG, L.P., Sabine Pass Liquefaction, LLC; Notice of Availability... Sabine Pass Sabine Pass LNG, L.P. and Sabine Pass Liquefaction, LLC (Sabine Pass) in the above-referenced... construction at the existing Sabine Pass LNG terminal in Cameron Parish, Louisiana. The EA assesses the...

  7. [Inactivated poliovirus vaccines: an inevitable choice for eliminating poliomyelitis].

    PubMed

    Vidor, J D; Jean-Denis, Shu

    2016-12-06

    The inactivated poliovirus vaccine (IPV) is a very old tool in the fight against poliomyelitis. Though supplanted by oral poliovirus vaccine (OPV) in the 1960s and 1970s, the IPV has now become an inevitable choice because of the increasingly recognized risks associated with continuous use of OPVs. Following the pioneering work of Jonas Salk, who established key principles for the IPV, considerable experience has accumulated over the years. This work has led to modern Salk IPV-containing vaccines, based on the use of inactivated wildtype polioviruses, which have been deployed for routine use in many countries. Very good protection against paralysis is achieved with IPV through the presence of circulating antibodies able to neutralize virus infectivity toward motor neurons. In addition, with IPV, a variable degree of protection against mucosal infection (and therefore transmission) through mucosal antibodies and immune cells is achieved, depending on previous exposure of subjects to wildtype or vaccine polioviruses. The use of an IPV-followed-by-OPV sequential immunization schedule has the potential advantage of eliminating the vaccine-associated paralytic poliomyelitis (VAPP) risk, while limiting the risks of vaccine-derived poliovirus (VDPVs). Sabin strain-derived IPVs are new tools, only recently beginning to be deployed, and data are being generated to document their performance. IPVs will play an irreplaceable role in global eradication of polio.

  8. Cold-adapted poliovirus mutants bypass a postentry replication block.

    PubMed

    Dove, A W; Racaniello, V R

    1997-06-01

    In the current model of poliovirus entry, the initial interaction of the native virion with its cellular receptor is followed by a transition to an altered form, which then acts as an intermediate in viral entry. While the native virion sediments at 160S in a sucrose gradient, the altered particle sediments at 135S, has lost the coat protein VP4, and has become more hydrophobic. Altered particles can be found both associated with cells and in the culture medium. It has been hypothesized that the cell-associated 135S particle releases the viral genome into the cell cytoplasm and that nonproductive transitions to the 135S form are responsible for the high particle-to-PFU ratio observed for polioviruses. At 25 degrees C, a temperature at which the transition to 135S particles does not occur, the P1/Mahoney strain of poliovirus was unable to replicate, and cold-adapted (ca) mutants were selected from the population. These mutants have not gained the ability to convert to 135S particles at 25 degrees C, and the block to wild-type (wt) infection at low temperatures is not at the level of cellular entry. The particle-to-PFU ratio of poliovirus does not change at 25 degrees C in the absence of alteration. Three independent amino acid changes in the 2C coding region were identified in ca mutants, at positions 218 (Val to Ile), 241 (Arg to Ala), and 309 (Met to Val). Introduction of any of these mutations individually into wt poliovirus by site-directed mutagenesis confers the ca phenotype. All three serotypes of the Sabin vaccine strains and the P3/Leon strain of poliovirus also exhibit the ca phenotype. These results do not support a model of poliovirus entry into cells that includes an obligatory transition to the 135S particle.

  9. Poliovirus surveillance by examining sewage specimens. Quantitative recovery of virus after introduction into sewerage at remote upstream location.

    PubMed

    Hovi, T; Stenvik, M; Partanen, H; Kangas, A

    2001-08-01

    In order to assess the feasibility of environmental poliovirus surveillance, known amounts of poliovirus type 1, strain Sabin, were flushed into the sewage network of Helsinki. Grab specimens collected at a remote downstream location and concentrated about a 100-fold revealed infectious poliovirus on four successive days in all three separate experiments. As for concentration, a simple two-phase separation method was found to be at least as useful as a several-fold more resource-demanding polyethylene glycol (PEG) precipitation method. Recovery of the introduced virus was remarkably high (more than 10%). Using the current system, it might be possible to detect poliovirus circulation in a population of 700,000 people by examining a single 400 ml sewage specimen, if 1 out of 10,000 inhabitants were excreting the virus. It is concluded that environmental surveillance is a sensitive approach to monitor silent poliovirus circulation in populations served by a sewage network.

  10. Poliovirus surveillance by examining sewage specimens. Quantitative recovery of virus after introduction into sewerage at remote upstream location.

    PubMed Central

    Hovi, T.; Stenvik, M.; Partanen, H.; Kangas, A.

    2001-01-01

    In order to assess the feasibility of environmental poliovirus surveillance, known amounts of poliovirus type 1, strain Sabin, were flushed into the sewage network of Helsinki. Grab specimens collected at a remote downstream location and concentrated about a 100-fold revealed infectious poliovirus on four successive days in all three separate experiments. As for concentration, a simple two-phase separation method was found to be at least as useful as a several-fold more resource-demanding polyethylene glycol (PEG) precipitation method. Recovery of the introduced virus was remarkably high (more than 10%). Using the current system, it might be possible to detect poliovirus circulation in a population of 700,000 people by examining a single 400 ml sewage specimen, if 1 out of 10,000 inhabitants were excreting the virus. It is concluded that environmental surveillance is a sensitive approach to monitor silent poliovirus circulation in populations served by a sewage network. PMID:11561962

  11. Environmental Surveillance of Polioviruses in Rio de Janeiro, Brazil, in Support to the Activities of Global Polio Eradication Initiative.

    PubMed

    de Oliveira Pereira, Joseane Simone; da Silva, Lidiane Rodrigues; de Meireles Nunes, Amanda; de Souza Oliveira, Silas; da Costa, Eliane Veiga; da Silva, Edson Elias

    2016-03-01

    Wild polioviruses still remain endemic in three countries (Afghanistan, Pakistan, and Nigeria) and re-emergency of wild polio has been reported in previously polio-free countries. Environmental surveillance has been used as a supplementary tool in monitoring the circulation of wild poliovirus (PVs) and/or vaccine-derived PVs even in the absence of acute flaccid paralysis cases. This study aimed to monitor the presence of polioviruses in wastewater samples collected at one wastewater treatment plant located in the municipality of Rio de Janeiro, Brazil. From December 2011 to June 2012 and from September to December 2012, 31 samples were collected and processed. RD and L20B cell cultures were able to isolate PVs and non-polio enteroviruses in 27/31 samples. Polioviruses were isolated in eight samples (type 1 Sabin = 1, type 2 Sabin = 5, and type 3 Sabin = 2). Vaccine-derived polioviruses were not detected nor evidence of recombination with other PVs or non-polio enterovirus serotypes were observed among the isolates. The Sabin-related serotypes 2 and 3 presented nucleotide substitutions in positions associated with the neurovirulent phenotype at the 5'-UTR. Changes in important Amino acid residues at VP1 were also observed in the serotypes 2 and 3. Environmental surveillance has been used successfully in monitoring the circulation of PVs and non-polio enteroviruses and it is of crucial importance in the final stages of the WHO global polio eradication initiative. Our results show the continuous circulation of Sabin-like PVs and non-polio enteroviruses in the analyzed area during the study period.

  12. [Absence of poliovirus circulation in Colombian departments with vaccination coverage below 80%].

    PubMed

    González, María Mercedes; Sarmiento, Luis; Rey-Benito, Gloria Janneth; Padilla, Leonardo; Giraldo, Alejandra María; Castaño, Jhon Carlos

    2012-08-01

    This study aims to explore a possible silent circulation of wild and vaccine-derived polioviruses in departments of Colombia with polio vaccination coverage of below 80%. The study collected 52 samples of wastewater concentrated as a result of precipitation with polyethylene glycol and sodium chloride. The viral detection was carried out through isolation and the identification through neutralization of the cytopathic effect, as well as through a conventional polymerase chain reaction following reverse transcription. The isolated polioviruses were characterized by the VP1 gene sequence. In two of the 52 samples, there was a presence of the Sabin type 2 poliovirus with more than 99% sequence similarity with the Sabin type 2 strain polio. Circulation of the nonpolio enterovirus was detected in 17.3% of the samples. The serotypes identified corresponded to coxsackievirus B1, echovirus 30, and echovirus 11. No evidence of the spread of either vaccine-derived poliovirus or wild poliovirus was detected in the departments of Colombia with polio coverage lower than 80%.

  13. An Introduction to Poliovirus: Pathogenesis, Vaccination, and the Endgame for Global Eradication.

    PubMed

    Minor, Philip D

    2016-01-01

    Poliomyelitis is caused by poliovirus, which is a positive strand non-enveloped virus that occurs in three distinct serotypes (1, 2, and 3). Infection is mainly by the fecal-oral route and can be confined to the gut by antibodies induced either by vaccine, previous infection or maternally acquired. Vaccines include the live attenuated strains developed by Sabin and the inactivated vaccines developed by Salk; the live attenuated vaccine (Oral Polio Vaccine or OPV) has been the main tool in the Global Program of Polio eradication of the World Health Organisation. Wild type 2 virus has not caused a case since 1999 and type 3 since 2012 and eradication seems near. However most infections are entirely silent so that sophisticated environmental surveillance may be needed to ensure that the virus has been eradicated, and the live vaccine can sometimes revert to virulent circulating forms under conditions that are not wholly understood. Cessation of vaccination is therefore an increasingly important issue and inactivated polio vaccine (IPV) is playing a larger part in the end game.

  14. Inactivation of poliovirus by gamma irradiation of wastewater sludges.

    PubMed

    Kaupert, N; Burgi, E; Scolaro, L

    1999-01-01

    The effect of gamma radiation on poliovirus infectivity seeded in sludge samples was investigated in order to determine the radiation dose required to inactivate 90% of viral infectivity (D10). Sludges were obtained from anaerobic pretreated sewages produced by San Felipe, a wastewater treatment facility located at the Tucuman province, Argentina. A D10 of 3.34 kGy was determined for poliovirus type III, Sabin strain, suspended in sludge samples. This value dropped to 1.92 kGy when the virus was suspended in water. A virucidal effect associated to sludges was also demonstrated. These results will be of interest when considering the dose of gamma radiation to be applied to wastewater sludges in order to preserve the environment from viral contamination.

  15. Guidance for Assessment of Poliovirus Vaccination Status and Vaccination of Children Who Have Received Poliovirus Vaccine Outside the United States.

    PubMed

    Marin, Mona; Patel, Manisha; Oberste, Steve; Pallansch, Mark A

    2017-01-13

    In 1988, the World Health Assembly resolved to eradicate poliomyelitis (polio). Since then, wild poliovirus (WPV) cases have declined by >99.9%, from an estimated 350,000 cases of polio each year to 74 cases in two countries in 2015 (1). This decrease was achieved primarily through the use of trivalent oral poliovirus vaccine (tOPV), which contains types 1, 2, and 3 live, attenuated polioviruses. Since 2000, the United States has exclusively used inactivated polio vaccine (IPV), which contains all three poliovirus types (2,3). In 2013, the World Health Organization (WHO) set a target of a polio-free world by 2018 (4). Of the three WPV types, type 2 was declared eradicated in September 2015. To remove the risk for infection with circulating type 2 vaccine-derived polioviruses (cVDPV), which can lead to paralysis similar to that caused by WPV, all OPV-using countries simultaneously switched in April 2016 from tOPV to bivalent OPV (bOPV), which contains only types 1 and 3 polioviruses (5). This report summarizes current Advisory Committee on Immunization Practices (ACIP) recommendations for poliovirus vaccination and provides CDC guidance, in the context of the switch from tOPV to bOPV, regarding assessment of vaccination status and vaccination of children who might have received poliovirus vaccine outside the United States, to ensure that children living in the United States (including immigrants and refugees) are protected against all three poliovirus types. This guidance is not new policy and does not change the recommendations of ACIP for poliovirus vaccination in the United States. Children living in the United States who might have received poliovirus vaccination outside the United States should meet ACIP recommendations for poliovirus vaccination, which require protection against all three poliovirus types by age-appropriate vaccination with IPV or tOPV. In the absence of vaccination records indicating receipt of these vaccines, only vaccination or

  16. 75 FR 68347 - Sabine Pass Liquefaction LLC, and Sabine Pass LNG, L.P.; Notice of Intent To Prepare an...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-05

    ... Energy Regulatory Commission Sabine Pass Liquefaction LLC, and Sabine Pass LNG, L.P.; Notice of Intent To... facilities by Sabine Pass Liquefaction LLC, and Sabine Pass LNG, L.P. (collectively referred to as Sabine... responsibilities. DOE proposes to authorize Sabine Pass Liquefaction, LLC to export liquefied natural gas...

  17. 77 FR 277 - Sabine Pass Liquefaction, LLC and Sabine Pass LNG, L.P; Notice of Availability of the...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-04

    ... Energy Regulatory Commission Sabine Pass Liquefaction, LLC and Sabine Pass LNG, L.P; Notice of... Sabine Pass LNG, L.P. (collectively referred to as Sabine Pass) in the above-referenced docket. Sabine... exportation of natural gas at the existing Sabine Pass LNG Import Terminal in Cameron Parish, Louisiana. The...

  18. 33 CFR 110.196 - Sabine Pass Channel, Sabine Pass, Tex.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Sabine Pass Channel, Sabine Pass, Tex. 110.196 Section 110.196 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Anchorage Grounds § 110.196 Sabine Pass Channel, Sabine Pass,...

  19. 33 CFR 110.196 - Sabine Pass Channel, Sabine Pass, Tex.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Sabine Pass Channel, Sabine Pass, Tex. 110.196 Section 110.196 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Anchorage Grounds § 110.196 Sabine Pass Channel, Sabine Pass,...

  20. 33 CFR 110.196 - Sabine Pass Channel, Sabine Pass, Tex.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 1 2014-07-01 2014-07-01 false Sabine Pass Channel, Sabine Pass, Tex. 110.196 Section 110.196 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Anchorage Grounds § 110.196 Sabine Pass Channel, Sabine Pass, Tex...

  1. 33 CFR 110.196 - Sabine Pass Channel, Sabine Pass, Tex.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 1 2013-07-01 2013-07-01 false Sabine Pass Channel, Sabine Pass, Tex. 110.196 Section 110.196 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Anchorage Grounds § 110.196 Sabine Pass Channel, Sabine Pass, Tex...

  2. 33 CFR 165.819 - Security Zone; Sabine Bank Channel, Sabine Pass Channel and Sabine-Neches Waterway, TX.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Sabine-Neches Waterway, TX. (a) Location. (1) The following LNG facility mooring basins are designated as fixed security zones whenever LNG carriers are moored within them: (i) Golden Pass LNG, Sabine TX: All...°45′50″ N, 093°55′17″ W. (ii) Sabine Pass LNG, Cameron Parish, LA: All mooring basin waters north of...

  3. 33 CFR 165.819 - Security Zone; Sabine Bank Channel, Sabine Pass Channel and Sabine-Neches Waterway, TX.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Sabine-Neches Waterway, TX. (a) Location. (1) The following LNG facility mooring basins are designated as fixed security zones whenever LNG carriers are moored within them: (i) Golden Pass LNG, Sabine TX: All...°45′50″ N, 093°55′17″ W. (ii) Sabine Pass LNG, Cameron Parish, LA: All mooring basin waters north of...

  4. 33 CFR 165.819 - Security Zone; Sabine Bank Channel, Sabine Pass Channel and Sabine-Neches Waterway, TX.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Sabine-Neches Waterway, TX. (a) Location. (1) The following LNG facility mooring basins are designated as fixed security zones whenever LNG carriers are moored within them: (i) Golden Pass LNG, Sabine TX: All...°45′50″ N, 093°55′17″ W. (ii) Sabine Pass LNG, Cameron Parish, LA: All mooring basin waters north of...

  5. 78 FR 62344 - Sabine Pass Liquefaction Expansion, LLC, Sabine Pass Liquefaction, LLC, and Sabine Pass LNG, L.P...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-18

    ... Sabine Pass LNG, L.P., Cheniere Creole Trail Pipeline, L.P.; Notice of Application Take notice that on... LNG, L.P. (collectively referred to as Sabine Pass) filed with the Federal Energy Regulatory..., construct, and operate additional liquefied natural gas (LNG) export facilities at the Sabine Pass LNG...

  6. 33 CFR 117.981 - Sabine River.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Sabine River. 117.981 Section 117.981 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS Specific Requirements Texas § 117.981 Sabine River. See § 117.493, Sabine River...

  7. High resolution identity testing of inactivated poliovirus vaccines

    PubMed Central

    Mee, Edward T.; Minor, Philip D.; Martin, Javier

    2015-01-01

    Background Definitive identification of poliovirus strains in vaccines is essential for quality control, particularly where multiple wild-type and Sabin strains are produced in the same facility. Sequence-based identification provides the ultimate in identity testing and would offer several advantages over serological methods. Methods We employed random RT-PCR and high throughput sequencing to recover full-length genome sequences from monovalent and trivalent poliovirus vaccine products at various stages of the manufacturing process. Results All expected strains were detected in previously characterised products and the method permitted identification of strains comprising as little as 0.1% of sequence reads. Highly similar Mahoney and Sabin 1 strains were readily discriminated on the basis of specific variant positions. Analysis of a product known to contain incorrect strains demonstrated that the method correctly identified the contaminants. Conclusion Random RT-PCR and shotgun sequencing provided high resolution identification of vaccine components. In addition to the recovery of full-length genome sequences, the method could also be easily adapted to the characterisation of minor variant frequencies and distinction of closely related products on the basis of distinguishing consensus and low frequency polymorphisms. PMID:26049003

  8. High resolution identity testing of inactivated poliovirus vaccines.

    PubMed

    Mee, Edward T; Minor, Philip D; Martin, Javier

    2015-07-09

    Definitive identification of poliovirus strains in vaccines is essential for quality control, particularly where multiple wild-type and Sabin strains are produced in the same facility. Sequence-based identification provides the ultimate in identity testing and would offer several advantages over serological methods. We employed random RT-PCR and high throughput sequencing to recover full-length genome sequences from monovalent and trivalent poliovirus vaccine products at various stages of the manufacturing process. All expected strains were detected in previously characterised products and the method permitted identification of strains comprising as little as 0.1% of sequence reads. Highly similar Mahoney and Sabin 1 strains were readily discriminated on the basis of specific variant positions. Analysis of a product known to contain incorrect strains demonstrated that the method correctly identified the contaminants. Random RT-PCR and shotgun sequencing provided high resolution identification of vaccine components. In addition to the recovery of full-length genome sequences, the method could also be easily adapted to the characterisation of minor variant frequencies and distinction of closely related products on the basis of distinguishing consensus and low frequency polymorphisms. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  9. Prolonged excretion of type-2 poliovirus from a primary immune deficient patient during the transition to a type-2 poliovirus-free world, Israel, 2016

    PubMed Central

    Weil, Merav; Shulman, Lester M; Heiman, Sophia; Stauber, Tali; Alfandari, Jacqueline; Weiss, Leah; Silberstein, Ilana; Indenbaum, Viki; Mendelson, Ella; Sofer, Danit

    2016-01-01

    Wild poliovirus type-2 has been eradicated, use of live type-2 vaccine has been terminated globally, and all type-2 polioviruses are under strict laboratory containment protocols. Re-emergence may arise from prolonged asymptomatic excretion of poliovirus by hospitalised primary immune deficient (PID) patients, as described here, through repeated exposure of close contacts to high titres of infected material. At this transition time, PID patients should be screened and hospital containment protocols updated in parallel with laboratory containment. PMID:27918258

  10. Transformation and Tumorigenicity Testing of Simian Cell Lines and Evaluation of Poliovirus Replication

    PubMed Central

    Dotti, Silvia; Lombardo, Tina; Villa, Riccardo; Cacciamali, Andrea; Zanotti, Cinzia; Andreani, Nadia Andrea; Cinotti, Stefano; Ferrari, Maura

    2017-01-01

    The key role of cell cultures in different scientific fields is worldwide recognized, both as in vitro research models alternative to laboratory animals and substrates for biological production. However, many safety concerns rise from the use of animal/human cell lines that may be tumorigenic, leading to potential adverse contaminations in cell-derived biologicals. In order to evaluate the suitability of 13 different cell lines for Poliovirus vaccine production, safety and quality, in vitro/in vivo tumorigenicity and Poliovirus propagation properties were evaluated. Our results revealed that non-human primate cell lines CYNOM-K1, FRhK-4, 4MBr-5 and 4647 are free of tumorigenic features and represent highly susceptible substrates for attenuated Sabin Poliovirus strains. In particular, FRhK-4 and 4647 cell lines are characterized by a higher in vitro replication, resulting indicated for the use in large-scale production field. PMID:28046048

  11. Prolonged Replication of a Type 1 Vaccine-Derived Poliovirus in an Immunodeficient Patient

    PubMed Central

    Kew, Olen M.; Sutter, Roland W.; Nottay, Baldev K.; McDonough, Michael J.; Prevots, D. Rebecca; Quick, Linda; Pallansch, Mark A.

    1998-01-01

    VP1 sequences were determined for poliovirus type 1 isolates obtained over a 189-day period from a poliomyelitis patient with common variable immunodeficiency syndrome (a defect in antibody formation). The isolate from the first sample, taken 11 days after onset of paralysis, contained two poliovirus populations, differing from the Sabin 1 vaccine strain by ∼10%, differing from diverse type 1 wild polioviruses by 19 to 24%, and differing from each other by 5.5% of nucleotides. Specimens taken after day 11 appeared to contain only one major poliovirus population. Evolution of VP1 sequences at synonymous third-codon positions occurred at an overall rate of ∼3.4% per year over the 189-day period. Assuming this rate to be constant throughout the period of infection, the infection was calculated to have started ∼9.3 years earlier. This estimate is about the time (6.9 years earlier) the patient received his last oral poliovirus vaccine dose, approximately 2 years before the diagnosis of immunodeficiency. These findings may have important implications for the strategy to eliminate poliovirus immunization after global polio eradication. PMID:9738040

  12. Bioinformatics analysis and genetic diversity of the poliovirus.

    PubMed

    Liu, Yanhan; Ma, Tengfei; Liu, Jianzhu; Zhao, Xiaona; Cheng, Ziqiang; Guo, Huijun; Wang, Shujing; Xu, Ruixue

    2014-12-01

    Poliomyelitis, a disease which can manifest as muscle paralysis, is caused by the poliovirus, which is a human enterovirus and member of the family Picornaviridae that usually transmits by the faecal-oral route. The viruses of the OPV (oral poliovirus attenuated-live vaccine) strains can mutate in the human intestine during replication and some of these mutations can lead to the recovery of serious neurovirulence. Informatics research of the poliovirus genome can be used to explain further the characteristics of this virus. In this study, sequences from 100 poliovirus isolates were acquired from GenBank. To determine the evolutionary relationship between the strains, we compared and analysed the sequences of the complete poliovirus genome and the VP1 region. The reconstructed phylogenetic trees for the complete sequences and the VP1 sequences were both divided into two branches, indicating that the genetic relationships of the whole poliovirus genome and the VP1 sequences are very similar. This branching indicates that the virulence and pathogenicity of poliomyelitis may be associated with the VP1 region. Sequence alignment of the VP1 region revealed numerous mutation sites in which mutation rates of >30 % were detected. In a group of strains recorded in the USA, mutation sites and mutation types were the same and this may be associated with their distribution in the evolutionary tree and their genetic relationship. In conclusion, the genetic evolutionary relationships of poliovirus isolate sequences are determined to a great extent by the VP1 protein, and poliovirus strains located on the same branch of the phylogenetic tree contain the same mutation spots and mutation types. Hence, the genetic characteristics of the VP1 region in the poliovirus genome should be analysed to identify the transmission route of poliovirus and provide the basis of viral immunity development.

  13. Outbreak of Type 2 Vaccine-Derived Poliovirus in Nigeria: Emergence and Widespread Circulation in an Underimmunized Population

    PubMed Central

    Pate, Muhammad Ali; Wannemuehler, Kathleen; Jenks, Julie; Burns, Cara; Chenoweth, Paul; Abanida, Emmanuel Ade; Adu, Festus; Baba, Marycelin; Gasasira, Alex; Iber, Jane; Mkanda, Pascal; Williams, A. J.; Shaw, Jing; Pallansch, Mark; Kew, Olen

    2011-01-01

    Wild poliovirus has remained endemic in northern Nigeria because of low coverage achieved in the routine immunization program and in supplementary immunization activities (SIAs). An outbreak of infection involving 315 cases of type 2 circulating vaccine-derived poliovirus (cVDPV2; >1% divergent from Sabin 2) occurred during July 2005–June 2010, a period when 23 of 34 SIAs used monovalent or bivalent oral poliovirus vaccine (OPV) lacking Sabin 2. In addition, 21 “pre-VDPV2” (0.5%–1.0% divergent) cases occurred during this period. Both cVDPV and pre-VDPV cases were clinically indistinguishable from cases due to wild poliovirus. The monthly incidence of cases increased sharply in early 2009, as more children aged without trivalent OPV SIAs. Cumulative state incidence of pre-VDPV2/cVDPV2 was correlated with low childhood immunization against poliovirus type 2 assessed by various means. Strengthened routine immunization programs in countries with suboptimal coverage and balanced use of OPV formulations in SIAs are necessary to minimize risks of VDPV emergence and circulation. PMID:21402542

  14. 77 FR 65546 - Sabine Pass Liquefaction, LLC; Sabine Pass LNG, L.P.; Notice of Petition To Amend Authorizations...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-29

    ... Energy Regulatory Commission Sabine Pass Liquefaction, LLC; Sabine Pass LNG, L.P.; Notice of Petition To... Pass Liquefaction, LLC and Sabine Pass LNG, L.P. (collectively, Sabine Pass), 700 Milam Street, Suite... and operate certain related facilities (Modification Project) at the existing Sabine Pass LNG...

  15. 76 FR 9573 - Sabine Pass Liquefaction, LLC and Sabine Pass LNG, L.P.; Notice of Application

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-18

    ... Energy Regulatory Commission Sabine Pass Liquefaction, LLC and Sabine Pass LNG, L.P.; Notice of Application Take notice that on January 31, 2011, Sabine Pass Liquefaction, LLC and Sabine Pass LNG, L.P... (Liquefaction Project) at the existing Sabine Pass LNG Terminal, located in Cameron Parish, Louisiana....

  16. Molecular characterization of poliovirus isolates from children who contracted vaccine-associated paralytic poliomyelitis (VAPP) following administration of monovalent type 3 oral poliovirus vaccine in the 1960s in Hungary.

    PubMed

    Kapusinszky, Beatrix; Molnár, Zsuzsanna; Szomor, Katalin N; Berencsi, György

    2010-03-01

    Hungarian children were immunized with monovalent oral poliovaccine (mOPV) delivered at 6-week intervals in the order Sabin 1, Sabin 3, Sabin 2, from 1959 until 1992. During that period, 90 cases of vaccine-associated paralytic poliomyelitis (VAPP) were reported, 52 of which were associated with Sabin 3-related virus (76% of VAPP cases with virologic data). Because of renewed interest in type 3 mOPV (mOPV3), molecular methods were used to reanalyze 18 of the Sabin 3-related isolates from 15 VAPP patients, confirming the original identification. All isolates had the U472C 5'-untranslated region (5'-UTR) substitution associated with reversion to neurovirulence, and from zero to seven nucleotide substitutions in the virus protein 1 (VP1) region. No evidence was found for prolonged mOPV3 replication in the VAPP patients or for spread of Sabin 3-related viruses beyond close vaccinee contacts. The VAPP diseases were prevented by a single dose of inactivated poliovirus vaccine from 1992 to 2006 in Hungary, as proved by continuous surveillance of acute flaccid paralysis.

  17. Production of high titer attenuated poliovirus strains on the serum-free PER.C6(®) cell culture platform for the generation of safe and affordable next generation IPV.

    PubMed

    Sanders, Barbara P; Oakes, Isabel de los Rios; van Hoek, Vladimir; Liu, Ying; Marissen, Wilfred; Minor, Philip D; Wimmer, Eckard; Schuitemaker, Hanneke; Custers, Jerome H H V; Macadam, Andrew; Cello, Jeronimo; Edo-Matas, Diana

    2015-11-27

    As poliovirus eradication draws closer, alternative Inactivated Poliovirus Vaccines (IPV) are needed to overcome the risks associated with continued use of the Oral Poliovirus Vaccine and of neurovirulent strains used during manufacture of conventional (c) IPV. We have previously demonstrated the susceptibility of the PER.C6(®) cell line to cIPV strains; here we investigated the suspension cell culture platform for growth of attenuated poliovirus strains. We examined attenuated Sabin strain productivity on the PER.C6(®) cell platform compared to the conventional Vero cell platform. The suitability of the suspension cell platform for propagation of rationally-attenuated poliovirus strains (stabilized Sabin type 3 S19 derivatives and genetically attenuated and stabilized MonoCre(X) strains), was also assessed. Yields were quantified by infectious titer determination and D-antigen ELISA using either serotype-specific polyclonal rabbit sera for Sabin strains or monoclonal cIPV-strain-specific antibodies for cIPV, S19 and MonoCre(X) strains. PER.C6(®) cells supported the replication of Sabin strains to yields of infectious titers that were in the range of cIPV strains at 32.5°C. Sabin strains achieved 30-fold higher yields (p<0.0001) on the PER.C6(®) cell platform as compared to the Vero cell platform in infectious titer and D-antigen content. Furthermore, Sabin strain productivity on the PER.C6(®) cell platform was maintained at 10l scale. Yields of infectious titers of S19 and MonoCre(X) strains were 0.5-1 log10 lower than seen for cIPV strains, whereas D-antigen yield and productivities in doses/ml using rationally-attenuated strains were in line with yields reported for cIPV strains. Sabin and rationally-attenuated polioviruses can be grown to high infectious titers and D-antigen yields. Sabin strain infection shows increased productivity on the PER.C6(®) cell platform as compared to the conventional Vero cell platform. Novel cell platforms with the potential

  18. 76 FR 14647 - Sabine National Forest Resource Advisory Committee Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-17

    ...; ] DEPARTMENT OF AGRICULTURE Sabine National Forest Resource Advisory Committee Meeting AGENCY: Forest Service, USDA. ACTION: Notice of Public Meeting, Sabine National Forest Resource Advisory Committee. SUMMARY: In.... Department of Agriculture, Forest Service, Sabine National Forest Resource Advisory Committee (RAC) meeting...

  19. Development of real-time PCR to detect oral vaccine-like poliovirus and its application to environmental surveillance.

    PubMed

    Iwai-Itamochi, Masae; Yoshida, Hiromu; Obara-Nagoya, Mayumi; Horimoto, Eiji; Kurata, Takeshi; Takizawa, Takenori

    2014-01-01

    In order to perform environmental surveillance to track oral poliovirus vaccine-like poliovirus sensitively and conveniently, real-time PCR was developed and applied to a raw sewage concentrate. The real-time PCR method detected 0.01-0.1 TCID50 of 3 serotypes of Sabin strain specifically. The method also detected the corresponding serotypes of oral poliovirus vaccine-like poliovirus specifically, but detected neither wild poliovirus, except Mahoney for type 1 and Saukett for type 3, nor other enteric viruses, as far as examined. When real-time PCR was applied to environmental surveillance, the overall agreement rates between real-time PCR and the cell culture were 83.3% for all serotypes. Since real-time PCR has the advantages of rapid detection of viruses and minimum requirement of sampling volume as compared with ordinary cell culture, it is suitable to monitor oral poliovirus vaccine-like poliovirus in the environment, especially in areas where an oral vaccine is being replaced by an inactivated vaccine.

  20. Identification and Analysis of Antiviral Compounds Against Poliovirus.

    PubMed

    Leyssen, Pieter; Franco, David; Tijsma, Aloys; Lacroix, Céline; De Palma, Armando; Neyts, Johan

    2016-01-01

    The Global Polio Eradication Initiative, launched in 1988, had as its goal the eradication of polio worldwide by the year 2000 through large-scale vaccinations campaigns with the live attenuated oral PV vaccine (OPV) (Griffiths et al., Biologicals 34:73-74, 2006). Despite substantial progress, polio remains endemic in several countries and new imported cases are reported on a regular basis ( http://www.polioeradication.org/casecount.asp ).It was recognized by the poliovirus research community that developing antivirals against poliovirus would be invaluable in the post-OPV era. Here, we describe three methods essential for the identification of selective inhibitors of poliovirus replication and for determining their mode of action by time-of-drug-addition studies as well as by the isolation of compound-resistant poliovirus variants.

  1. Poliovirus vaccination during the endgame: insights from integrated modeling.

    PubMed

    Duintjer Tebbens, Radboud J; Thompson, Kimberly M

    2017-06-01

    Managing the polio endgame requires access to sufficient quantities of poliovirus vaccines. After oral poliovirus vaccine (OPV) cessation, outbreaks may occur that require outbreak response using monovalent OPV (mOPV) and/or inactivated poliovirus vaccine. Areas covered: We review the experience and challenges with managing vaccine supplies in the context of the polio endgame. Building on models that explored polio endgame risks and the potential mOPV needs to stop outbreaks from live poliovirus reintroductions, we conceptually explore the potential demands for finished and bulk mOPV doses from a stockpile in the context of limited shelf-life of finished vaccine and time delays to convert bulk to finished vaccine. Our analysis suggests that the required size of the mOPV stockpile varies by serotype, with the highest expected needs for serotype 1 mOPV. Based on realizations of poliovirus risks after OPV cessation, the stockpile required to eliminate the chance of a stock-out appears considerably larger than the currently planned mOPV stockpiles. Expert commentary: The total required stockpile size depends on the acceptable probability of a stock-out, and increases with longer times to finish bulk doses and shorter shelf-lives of finished doses. Successful polio endgame management will require careful attention to poliovirus vaccine supplies.

  2. Assessment of areas at increased risk for poliovirus circulation in Ecuador.

    PubMed

    Dayan, Gustavo H; Rodríguez, Rodrigo; Vinjé, Jan; Vásconez, Nancy; Cáceres, Víctor; Gregoricus, Nicole; Sobsey, Mark; Landaverde, Mauricio

    2004-10-01

    To assess areas at risk for poliovirus circulation in Ecuador, we first selected provinces at highest risk based on low immunization coverage with three doses of oral poliovirus vaccine, and a low number of reported cases of acute flaccid paralysis (AFP). Subsequently, we reviewed discharge data for the period 1996--2000 for diagnoses compatible with AFP in the only two national referral hospitals in Quito, and at least two main hospitals in each of the six selected provinces. Environmental samples from one or two cities/towns in each selected province were tested for poliovirus. Of the 14 identified AFP-compatible cases, 8 (57%) had been previously reported and investigated. We visited four out of the six unreported cases; none of those four had sequelae compatible with poliomyelitis. From the 14 environmental samples taken, we identified Sabin viruses in six of the samples; no vaccine-derived polioviruses were isolated. Using this methodology, we found no evidence of undetected poliovirus circulation in Ecuador.

  3. An antigen chimera of poliovirus induces antibodies against human papillomavirus type 16.

    PubMed Central

    Jenkins, O; Cason, J; Burke, K L; Lunney, D; Gillen, A; Patel, D; McCance, D J; Almond, J W

    1990-01-01

    It has been established that the surface of poliovirus type 1 can be extensively modified to incorporate antigenic domains from other poliovirus serotypes and from unrelated viruses. The fact that the modified (chimeric) viruses exhibit dual antigenicity and immunogenicity led us to explore the possibility of using the Sabin vaccine strain of poliovirus type 1 as a vector for the presentation of antigenic domains from human papillomavirus type 16 (HPV-16), a virus associated with the development of cervical carcinoma. We report here the construction and characterization of a chimeric poliovirus containing a 16-residue sequence derived from the major capsid protein (L1) of HPV-16. This virus chimera stimulated the production in rabbits of antibodies which recognized the HPV-16-derived peptide and an L1 fusion protein synthesized in Escherichia coli and detected HPV-16 in human biopsy material by immunoperoxidase staining. The possibility that poliovirus-HPV chimeras could be used as vaccines against HPV-16 is discussed. Images PMID:2154604

  4. Assessment of areas at increased risk for poliovirus circulation in Ecuador.

    PubMed Central

    Dayan, Gustavo H.; Rodríguez, Rodrigo; Vinjé, Jan; Vásconez, Nancy; Cáceres, Víctor; Gregoricus, Nicole; Sobsey, Mark; Landaverde, Mauricio

    2004-01-01

    To assess areas at risk for poliovirus circulation in Ecuador, we first selected provinces at highest risk based on low immunization coverage with three doses of oral poliovirus vaccine, and a low number of reported cases of acute flaccid paralysis (AFP). Subsequently, we reviewed discharge data for the period 1996--2000 for diagnoses compatible with AFP in the only two national referral hospitals in Quito, and at least two main hospitals in each of the six selected provinces. Environmental samples from one or two cities/towns in each selected province were tested for poliovirus. Of the 14 identified AFP-compatible cases, 8 (57%) had been previously reported and investigated. We visited four out of the six unreported cases; none of those four had sequelae compatible with poliomyelitis. From the 14 environmental samples taken, we identified Sabin viruses in six of the samples; no vaccine-derived polioviruses were isolated. Using this methodology, we found no evidence of undetected poliovirus circulation in Ecuador. PMID:15473140

  5. 76 FR 1519 - Security Zones; Sabine Bank Channel, Sabine Pass Channel and Sabine-Neches Waterway, TX

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-11

    ... encompassing the mooring basins of LNG carriers while they are moored at the Golden Pass LNG facility in Sabine, TX and/or the Sabine Pass LNG facility located in Cameron Parish, LA. DATES: This rule is effective... Facility (M-30), U.S. Department of Transportation, West Building Ground Floor, Room W12-140, 1200 New...

  6. 75 FR 65232 - Security Zones; Sabine Bank Channel, Sabine Pass Channel and Sabine-Neches Waterway, TX

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-22

    ... measures necessary. In addition, it establishes security zones encompassing the mooring basins of LNG carriers while they are moored at the Golden Pass LNG facility in Sabine, TX and/or the Sabine Pass LNG...: Docket Management Facility (M-30), U.S. Department of Transportation, West Building Ground Floor, Room...

  7. 75 FR 29695 - Security Zones; Sabine Bank Channel, Sabine Pass Channel and Sabine-Neches Waterway, TX

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-27

    ... Guard proposes a 100-foot security zone around LNG carriers while they are moored at the Golden Pass LNG facility in Sabine, TX and/or the Sabine Pass LNG facility located in Cheniere, LA. DATES: Comments and... (M-30), U.S. Department of Transportation, West Building Ground Floor, Room W12-140, 1200 New Jersey...

  8. Transgenic mice as an alternative to monkeys for neurovirulence testing of live oral poliovirus vaccine: validation by a WHO collaborative study.

    PubMed Central

    Dragunsky, Eugenia; Nomura, Tatsuji; Karpinski, Kazimir; Furesz, John; Wood, David J.; Pervikov, Yuri; Abe, Shinobu; Kurata, Takeshi; Vanloocke, Olivier; Karganova, Galina; Taffs, Rolf; Heath, Alan; Ivshina, Anna; Levenbook, Inessa

    2003-01-01

    OBJECTIVE: Extensive WHO collaborative studies were performed to evaluate the suitability of transgenic mice susceptible to poliovirus (TgPVR mice, strain 21, bred and provided by the Central Institute for Experimental Animals, Japan) as an alternative to monkeys in the neurovirulence test (NVT) of oral poliovirus vaccine (OPV). METHODS: Nine laboratories participated in the collaborative study on testing neurovirulence of 94 preparations of OPV and vaccine derivatives of all three serotypes in TgPVR21 mice. FINDINGS: Statistical analysis of the data demonstrated that the TgPVR21 mouse NVT was of comparable sensitivity and reproducibility to the conventional WHO NVT in simians. A statistical model for acceptance/rejection of OPV lots in the mouse test was developed, validated, and shown to be suitable for all three vaccine types. The assessment of the transgenic mouse NVT is based on clinical evaluation of paralysed mice. Unlike the monkey NVT, histological examination of central nervous system tissue of each mouse offered no advantage over careful and detailed clinical observation. CONCLUSIONS: Based on data from the collaborative studies the WHO Expert Committee for Biological Standardization approved the mouse NVT as an alternative to the monkey test for all three OPV types and defined a standard implementation process for laboratories that wish to use the test. This represents the first successful introduction of transgenic animals into control of biologicals. PMID:12764491

  9. Mapping of sequences required for mouse neurovirulence of poliovirus type 2 Lansing.

    PubMed

    La Monica, N; Meriam, C; Racaniello, V R

    1986-02-01

    Intracerebral inoculation of mice with poliovirus type 2 Lansing induces a fatal paralysis, while most other poliovirus strains are unable to cause disease in the mouse. To determine the molecular basis for Lansing virus neurovirulence, we determined the complete nucleotide sequence of the Lansing viral genome from cloned cDNA. The deduced amino acid sequence was compared with that of two mouse-avirulent strains. There are 83 amino acid differences between the Lansing and Sabin type 2 strain and 179 differences between the Lansing and Mahoney type 1 strain scattered throughout the genome. To further localize Lansing sequences important for mouse neurovirulence, four intertypic recombinants were isolated by exchanging DNA restriction fragments between the Lansing 2 and Mahoney 1 infectious poliovirus cDNA clones. Plasmids were transfected into HeLa cells, and infectious recombinant viruses were recovered. All four recombinant viruses, which contained the Lansing capsid region and different amounts of the Mahoney genome, were neurovirulent for 18- to 21-day-old Swiss-Webster mice by the intracerebral route. The genome of neurovirulent recombinant PRV5.1 contained only nucleotides 631 to 3413 from Lansing, encoding primarily the viral capsid proteins. Therefore, the ability of Lansing virus to cause paralysis in mice is due to the viral capsid. The Lansing capsid sequence differs from that of the mouse avirulent Sabin 2 strain at 32 of 879 amino acid positions: 1 in VP4, 5 in VP2, 4 in VP3, and 22 in VP1.

  10. 33 CFR 117.979 - Sabine Lake.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Sabine Lake. 117.979 Section 117.979 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS Specific Requirements Texas § 117.979 Sabine Lake. The draw of the S82 bridge, mile 10...

  11. 33 CFR 117.493 - Sabine River.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Sabine River. 117.493 Section 117.493 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS Specific Requirements Louisiana § 117.493 Sabine River. (a) The draw of the Union...

  12. 33 CFR 117.493 - Sabine River.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Sabine River. 117.493 Section 117.493 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS Specific Requirements Louisiana § 117.493 Sabine River. (a) The draw of the Union...

  13. 33 CFR 117.493 - Sabine River.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 1 2014-07-01 2014-07-01 false Sabine River. 117.493 Section 117.493 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS Specific Requirements Louisiana § 117.493 Sabine River. (a) The draw of the Union...

  14. 33 CFR 117.493 - Sabine River.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 1 2013-07-01 2013-07-01 false Sabine River. 117.493 Section 117.493 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS Specific Requirements Louisiana § 117.493 Sabine River. (a) The draw of the Union...

  15. 33 CFR 117.493 - Sabine River.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 1 2012-07-01 2012-07-01 false Sabine River. 117.493 Section 117.493 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS Specific Requirements Louisiana § 117.493 Sabine River. (a) The draw of the Union...

  16. 76 FR 66033 - Sabine Resource Advisory Committee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-25

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF AGRICULTURE Forest Service Sabine Resource Advisory Committee AGENCY: Forest Service, USDA. ACTION: Notice of meeting cancellation. SUMMARY: The Sabine-Angelina Resource Advisory Committee was scheduled to meet October 20,...

  17. 33 CFR 117.979 - Sabine Lake.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 1 2014-07-01 2014-07-01 false Sabine Lake. 117.979 Section 117.979 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS Specific Requirements Texas § 117.979 Sabine Lake. The draw of the S82 bridge, mile 10...

  18. 33 CFR 117.979 - Sabine Lake.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 1 2013-07-01 2013-07-01 false Sabine Lake. 117.979 Section 117.979 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS Specific Requirements Texas § 117.979 Sabine Lake. The draw of the S82 bridge, mile 10...

  19. 33 CFR 117.979 - Sabine Lake.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 1 2012-07-01 2012-07-01 false Sabine Lake. 117.979 Section 117.979 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS Specific Requirements Texas § 117.979 Sabine Lake. The draw of the S82 bridge, mile 10...

  20. 76 FR 62342 - Sabine Resource Advisory Committee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-07

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF AGRICULTURE Forest Service Sabine Resource Advisory Committee AGENCY: Forest Service, USDA. ACTION: Notice of meeting. SUMMARY: The Sabine Resource Advisory Committee will meet in Hemphill, Texas. The committee is authorized...

  1. 77 FR 53842 - Sabine Resource Advisory Committee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-04

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF AGRICULTURE Forest Service Sabine Resource Advisory Committee AGENCY: Forest Service, USDA. ACTION: Notice of meeting. SUMMARY: The Sabine Resource Advisory Committee will meet in Hemphill, Texas. The committee is authorized...

  2. 76 FR 28950 - Sabine Resource Advisory Committee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-19

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF AGRICULTURE Sabine Resource Advisory Committee AGENCY: Forest Service, USDA. ACTION: Notice of meeting. SUMMARY: The Sabine Resource Advisory Committee will meet in Hemphill, Texas. The committee is authorized under the...

  3. World Health Organization Guidelines for Containment of Poliovirus Following Type-Specific Polio Eradication - Worldwide, 2015.

    PubMed

    Previsani, Nicoletta; Tangermann, Rudolph H; Tallis, Graham; Jafari, Hamid S

    2015-08-28

    In 1988, the World Health Assembly of the World Health Organization (WHO) resolved to eradicate polio worldwide. Among the three wild poliovirus (WPV) types (type 1, type 2, and type 3), WPV type 2 (WPV2) has been eliminated in the wild since 1999, and WPV type 3 (WPV3) has not been reported since 2012. In 2015, only Afghanistan and Pakistan have reported WPV transmission. On May 25, 2015, all WHO Member States endorsed World Health Assembly resolution 68.3 on full implementation of the Polio Eradication and Endgame Strategic Plan 2013-2018 (the Endgame Plan), and with it, the third Global Action Plan to minimize poliovirus facility-associated risk (GAPIII). All WHO Member States have committed to implementing appropriate containment of WPV2 in essential laboratory and vaccine production facilities* by the end of 2015 and of type 2 oral poliovirus vaccine (OPV2) within 3 months of global withdrawal of OPV2, which is planned for April 2016. This report summarizes critical steps for essential laboratory and vaccine production facilities that intend to retain materials confirmed to contain or potentially containing type-specific WPV, vaccine-derived poliovirus (VDPV), or OPV/Sabin viruses, and steps for nonessential facilities† that process specimens that contain or might contain polioviruses. National authorities will need to certify that the essential facilities they host meet the containment requirements described in GAPIII. After certification of WPV eradication, the use of all OPV will cease; final containment of all polioviruses after polio eradication and OPV cessation will minimize the risk for reintroduction of poliovirus into a polio-free world.

  4. Importation and circulation of poliovirus in Bulgaria in 2001.

    PubMed Central

    Kojouharova, Mira; Zuber, Patrick L. F.; Gyurova, Snejana; Fiore, Lucia; Buttinelli, Gabriele; Kunchev, Angel; Vladimirova, Nadejda; Korsun, Neli; Filipova, Radosveta; Boneva, Roumiana; Gavrilin, Eugene; Deshpande, Jagadish M.; Oblapenko, George; Wassilak, Steven G.

    2003-01-01

    OBJECTIVE: To characterize the circumstances in which poliomyelitis occurred among three children in Bulgaria during 2001 and to describe the public health response. METHODS: Bulgarian authorities investigated the three cases of polio and their contacts, conducted faecal and serological screening of children from high-risk groups, implemented enhanced surveillance for acute flaccid paralysis, and conducted supplemental immunization activities. FINDINGS: The three cases of polio studied had not been vaccinated and lived in socioeconomically deprived areas of two cities. Four Roma children from the Bourgas district had antibody titres to serotype 1 poliovirus only, and wild type 1 virus was isolated from the faeces of two asymptomatic Roma children in the Bourgas and Sofia districts. Poliovirus isolates were related genetically and represented a single evolutionary lineage; genomic sequences were less than 90% identical to poliovirus strains isolated previously in Europe, but 98.3% similar to a strain isolated in India in 2000. No cases or wild virus isolates were found after supplemental immunization activities were launched in May 2001. CONCLUSIONS: In Bulgaria, an imported poliovirus was able to circulate for two to five months among minority populations. Surveillance data strongly suggest that wild poliovirus circulation ceased shortly after supplemental immunization activities with oral poliovirus vaccine were conducted. PMID:12973639

  5. 78 FR 1851 - Sabine Pass Liquefaction, LLC and Sabine Pass LNG, L.P.; Notice of Intent To Prepare an...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-09

    ... Energy Regulatory Commission Sabine Pass Liquefaction, LLC and Sabine Pass LNG, L.P.; Notice of Intent To Prepare an Environmental Assessment for the Proposed Sabine Pass Liquefaction Modification Project and... impacts of the Sabine Pass Liquefaction Modification Project (Project) involving the modification of...

  6. Exchanges of genomic domains between poliovirus and other cocirculating species C enteroviruses reveal a high degree of plasticity

    PubMed Central

    Bessaud, Maël; Joffret, Marie-Line; Blondel, Bruno; Delpeyroux, Francis

    2016-01-01

    The attenuated Sabin strains contained in the oral poliomyelitis vaccine are genetically unstable, and their circulation in poorly immunized populations can lead to the emergence of pathogenic circulating vaccine-derived polioviruses (cVDPVs). The recombinant nature of most cVDPV genomes and the preferential presence of genomic sequences from certain cocirculating non-polio enteroviruses of species C (EV-Cs) raise questions about the permissiveness of genetic exchanges between EV-Cs and the phenotypic impact of such exchanges. We investigated whether functional constraints limited genetic exchanges between Sabin strains and other EV-Cs. We bypassed the natural recombination events by constructing 29 genomes containing a Sabin 2 capsid-encoding sequence and other sequences from Sabin 2 or from non-polio EV-Cs. Most genomes were functional. All recombinant viruses replicated similarly in vitro, but recombination modulated plaque size and temperature sensitivity. All viruses with a 5′UTR from Sabin 2 were attenuated in mice, whereas almost all viruses with a non-polio 5′UTR caused disease. These data highlight the striking conservation of functional compatibility between different genetic domains of cocirculating EV-Cs. This aspect is only one of the requirements for the generation of recombinant cVDPVs in natural conditions, but it may facilitate the generation of viable intertypic recombinants with diverse phenotypic features, including pathogenicity. PMID:27958320

  7. Limited and localized outbreak of newly emergent type 2 vaccine-derived poliovirus in Sichuan, China.

    PubMed

    Yan, Dongmei; Zhang, Yong; Zhu, Shuangli; Chen, Na; Li, Xiaolei; Wang, Dongyan; Ma, Xiaozhen; Zhu, Hui; Tong, Wenbin; Xu, Wenbo

    2014-07-01

    From August 2011 to February 2012, an outbreak caused by type 2 circulating vaccine-derived poliovirus (cVDPV) occurred in Aba County, Sichuan, China. During the outbreak, four type 2 VDPVs (≥0.6% nucleotide divergence in the VP1 region relative to the Sabin 2 strain) were isolated from 3 patients with acute flaccid paralysis (AFP) and one close contact. In addition, a type 2 pre-VDPV (0.3% to 0.5% divergence from Sabin 2) that was genetically related to these type 2 VDPVs was isolated from another AFP patient. These 4 patients were all unimmunized children 0.7 to 1.1 years old. Nucleotide sequencing revealed that the 4 VDPV isolates differed from Sabin 2 by 0.7% to 1.2% in nucleotides in the VP1 region and shared 5 nucleotide substitutions with the pre-VDPV. All 5 isolates were closely related, and all were S2/S3/S2/S3 recombinants sharing common recombination crossover sites. Although the two major determinants of attenuation and temperature sensitivity phenotype of Sabin 2 (A481 in the 5' untranslated region and Ile143 in the VP1 protein) had reverted in all 5 isolates, one VDPV (strain CHN16017) still retained the temperature sensitivity phenotype. Phylogenetic analysis of the third coding position of the complete P1 coding region suggested that the cVDPVs circulated locally for about 7 months following the initiating oral poliovirus vaccine (OPV) dose. Our findings reinforce the point that cVDPVs can emerge and spread in isolated communities with immunity gaps and highlight the emergence risks of type 2 cVDPVs accompanying the trivalent OPV used. To solve this issue, it is recommended that type 2 OPV be removed from the trivalent OPV or that inactivated polio vaccine (IPV) be used instead.

  8. Evolution of Circulating Wild Poliovirus and of Vaccine-Derived Poliovirus in an Immunodeficient Patient: a Unifying Model

    PubMed Central

    Gavrilin, Gene V.; Cherkasova, Elena A.; Lipskaya, Galina Y.; Kew, Olen M.; Agol, Vadim I.

    2000-01-01

    We determined nucleotide sequences of the VP1 and 2AB genes and portions of the 2C and 3D genes of two evolving poliovirus lineages: circulating wild viruses of T geotype and Sabin vaccine-derived isolates from an immunodeficient patient. Different regions of the viral RNA were found to evolve nonsynchronously, and the rate of evolution of the 2AB region in the vaccine-derived population was not constant throughout its history. Synonymous replacements occurred not completely randomly, suggesting the need for conservation of certain rare codons (possibly to control translation elongation) and the existence of unidentified constraints in the viral RNA structure. Nevertheless the major contribution to the evolution of the two lineages came from linear accumulation of synonymous substitutions. Therefore, in agreement with current theories of viral evolution, we suggest that the majority of the mutations in both lineages were fixed as a result of successive sampling, from the heterogeneous populations, of random portions containing predominantly neutral and possibly adverse mutations. As a result of such a mode of evolution, the virus fitness may be maintained at a more or less constant level or may decrease unless more-fit variants are stochastically generated. The proposed unifying model of natural poliovirus evolution has important implications for the epidemiology of poliomyelitis. PMID:10906191

  9. Managing population immunity to reduce or eliminate the risks of circulation following the importation of polioviruses.

    PubMed

    Thompson, Kimberly M; Kalkowska, Dominika A; Duintjer Tebbens, Radboud J

    2015-03-24

    Poliovirus importations into polio-free countries represent a major concern during the final phases of global eradication of wild polioviruses (WPVs). We extend dynamic transmission models to demonstrate the dynamics of population immunity out through 2020 for three countries that only used inactivated poliovirus vaccine (IPV) for routine immunization: the US, Israel, and The Netherlands. For each country, we explore the vulnerability to re-established transmission following an importation for each poliovirus serotype, including the impact of immunization choices following the serotype 1 WPV importation that occurred in 2013 in Israel. As population immunity declines below the threshold required to prevent transmission, countries become at risk for re-established transmission. Although importations represent stochastic events that countries cannot fully control because people cross borders and polioviruses mainly cause asymptomatic infections, countries can ensure that any importations die out. Our results suggest that the general US population will remain above the threshold for transmission through 2020. In contrast, Israel became vulnerable to re-established transmission of importations of live polioviruses by the late 2000s. In Israel, the recent WPV importation and outbreak response use of bivalent oral poliovirus vaccine (bOPV) eliminated the vulnerability to an importation of poliovirus serotypes 1 and 3 for several years, but not serotype 2. The Netherlands experienced a serotype 1 WPV outbreak in 1992-1993 and became vulnerable to re-established transmission in religious communities with low vaccine acceptance around the year 2000, although the general population remains well-protected from widespread transmission. All countries should invest in active management of population immunity to avoid the potential circulation of imported live polioviruses. IPV-using countries may wish to consider prevention opportunities and/or ensure preparedness for response

  10. S2M: A Stochastic Simulation Model of Poliovirus Genetic State Transition

    PubMed Central

    Ecale Zhou, Carol L.

    2016-01-01

    Modeling the molecular mechanisms that govern genetic variation can be useful in understanding the dynamics that drive genetic state transition in quasispecies viruses. For example, there is considerable interest in understanding how the relatively benign vaccine strains of poliovirus eventually revert to forms that confer neurovirulence and cause disease (ie, vaccine-derived poliovirus). This report describes a stochastic simulation model, S2M, which can be used to generate hypothetical outcomes based on known mechanisms of genetic diversity. S2M begins with predefined genotypes based on the Sabin-1 and Mahoney wild-type sequences, constructs a set of independent cell-based populations, and performs in-cell replication and cell-to-cell infection cycles while quantifying genetic changes that track the transition from Sabin-1 toward Mahoney. Realism is incorporated into the model by assigning defaults for variables that constrain mechanisms of genetic variability based roughly on metrics reported in the literature, yet these values can be modified at the command line in order to generate hypothetical outcomes driven by these parameters. To demonstrate the utility of S2M, simulations were performed to examine the effects of the rates of replication error and recombination and the presence or absence of defective interfering particles, upon reaching the end states of Mahoney resemblance (semblance of a vaccine-derived state), neurovirulence, genome fitness, and cloud diversity. Simulations provide insight into how modeled biological features may drive hypothetical outcomes, independently or in combination, in ways that are not always intuitively obvious. PMID:27385911

  11. S2M: A Stochastic Simulation Model of Poliovirus Genetic State Transition.

    PubMed

    Ecale Zhou, Carol L

    2016-01-01

    Modeling the molecular mechanisms that govern genetic variation can be useful in understanding the dynamics that drive genetic state transition in quasispecies viruses. For example, there is considerable interest in understanding how the relatively benign vaccine strains of poliovirus eventually revert to forms that confer neurovirulence and cause disease (ie, vaccine-derived poliovirus). This report describes a stochastic simulation model, S2M, which can be used to generate hypothetical outcomes based on known mechanisms of genetic diversity. S2M begins with predefined genotypes based on the Sabin-1 and Mahoney wild-type sequences, constructs a set of independent cell-based populations, and performs in-cell replication and cell-to-cell infection cycles while quantifying genetic changes that track the transition from Sabin-1 toward Mahoney. Realism is incorporated into the model by assigning defaults for variables that constrain mechanisms of genetic variability based roughly on metrics reported in the literature, yet these values can be modified at the command line in order to generate hypothetical outcomes driven by these parameters. To demonstrate the utility of S2M, simulations were performed to examine the effects of the rates of replication error and recombination and the presence or absence of defective interfering particles, upon reaching the end states of Mahoney resemblance (semblance of a vaccine-derived state), neurovirulence, genome fitness, and cloud diversity. Simulations provide insight into how modeled biological features may drive hypothetical outcomes, independently or in combination, in ways that are not always intuitively obvious.

  12. 76 FR 52563 - Special Local Regulations; Sabine River, Orange, TX

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-23

    ... SECURITY Coast Guard 33 CFR Part 100 RIN 1625-AA08 Special Local Regulations; Sabine River, Orange, TX...) entitled Special Local Regulations; Sabine River, Orange, TX in the Federal Register (76 FR 103). We... Events; Sabine River, Orange, TX. (a) Definitions. As used in this section ``Participant Vessel''...

  13. 75 FR 55968 - Special Local Regulations, Sabine River; Orange, TX

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-15

    ... SECURITY Coast Guard 33 CFR Part 100 RIN 1625-AA08 Special Local Regulations, Sabine River; Orange, TX... temporary Special Local Regulation in the Port Arthur Captain of the Port Zone on the Sabine River, Orange... (NPRM) entitled Special Local Regulations; Sabine River, Orange, TX in the Federal Register (75 FR 41119...

  14. An economic analysis of poliovirus risk management policy options for 2013-2052.

    PubMed

    Duintjer Tebbens, Radboud J; Pallansch, Mark A; Cochi, Stephen L; Wassilak, Steven G F; Thompson, Kimberly M

    2015-09-24

    positive net benefits of OPV cessation. Important uncertainties will require more research, including characterizing immunodeficient long-term poliovirus excretor risks, containment risks, and the kinetics of outbreaks and response in an unprecedented world without widespread live poliovirus exposure.

  15. Detection of Imported Wild Polioviruses and of Vaccine-Derived Polioviruses by Environmental Surveillance in Egypt

    PubMed Central

    El Bassioni, Laila; El Maamoon Nasr, Eman M.; Paananen, Anja; Kaijalainen, Svetlana; Asghar, Humayun; de Gourville, Esther; Roivainen, Merja

    2012-01-01

    Systematic environmental surveillance for poliovirus circulation has been conducted in Egypt since 2000. The surveillance has revealed three independent importations of wild-type poliovirus. In addition, several vaccine-derived polioviruses have been detected in various locations in Egypt. In addition to acute flaccid paralysis (AFP) surveillance, environmental surveillance can be used to monitor the wild poliovirus and vaccine-derived poliovirus circulation in populations in support of polio eradication initiatives. PMID:22582070

  16. Sensitivity of C6 Glioma Cells Carrying the Human Poliovirus Receptor to Oncolytic Polioviruses.

    PubMed

    Sosnovtseva, A O; Lipatova, A V; Grinenko, N F; Baklaushev, V P; Chumakov, P M; Chekhonin, V P

    2016-10-01

    A humanized line of rat C6 glioma cells expressing human poliovirus receptor was obtained and tested for the sensitivity to oncolytic effects of vaccine strains of type 1, 2, and 3 polioviruses. Presentation of the poliovirus receptor on the surface of C6 glioma cells was shown to be a necessary condition for the interaction of cells with polioviruses, but insufficient for complete poliovirus oncolysis.

  17. Characteristics of an environmentally monitored prolonged type 2 vaccine derived poliovirus shedding episode that stopped without intervention.

    PubMed

    Hovi, Tapani; Paananen, Anja; Blomqvist, Soile; Savolainen-Kopra, Carita; Al-Hello, Haider; Smura, Teemu; Shimizu, Hiroyuki; Nadova, Katarina; Sobotova, Zdenka; Gavrilin, Eugene; Roivainen, Merja

    2013-01-01

    Vaccine derived poliovirus (VDPV) type 2 strains strongly divergent from the corresponding vaccine strain, Sabin 2, were repeatedly isolated from sewage in Slovakia over a period of 22 months in 2003-2005. Cell cultures of stool specimens from known immune deficient patients and from an identified putative source population of 500 people failed to identify the potential excretor(s) of the virus. The occurrence of VDPV in sewage stopped without any intervention. No paralytic cases were reported in Slovakia during the episode. According to a GenBank search and similarity plotting-analysis, the closest known relative of the first isolate PV2/03/SVK/E783 through all main sections of the genome was the type 2 poliovirus Sabin strain, with nucleotide identities in 5'UTR, P1, P2, P3, and 3'UTR parts of the genome of 88.6, 85.9, 87.3, 88.5, and 94.0 percent, respectively. Phenotypic properties of selected Slovakian aVDPV strains resembled those of VDPV strains isolated from immune deficient individuals with prolonged PV infection (iVDPV), including antigenic changes and moderate neurovirulence in the transgenic mouse model. One hundred and two unique VP1 coding sequences were determined from VDPV strains isolated from 34 sewage specimens. Nucleotide differences from Sabin 2 in the VP1 coding region ranged from 12.5 to 15.6 percent, and reached a maximum of 9.6 percent between the VDPV strains under study. Most of the nucleotide substitutions were synonymous but as many as 93 amino acid positions out of 301 in VP1 showed substitutions. We conclude that (1) individuals with prolonged poliovirus infection are not as rare as suggested by the studies on immune deficient patients known to the health care systems and (2) genetic divergence of VDPV strains may remain extensive during years long replication in humans.

  18. Characteristics of an Environmentally Monitored Prolonged Type 2 Vaccine Derived Poliovirus Shedding Episode that Stopped without Intervention

    PubMed Central

    Hovi, Tapani; Paananen, Anja; Blomqvist, Soile; Savolainen-Kopra, Carita; Al-Hello, Haider; Smura, Teemu; Shimizu, Hiroyuki; Nadova, Katarina; Sobotova, Zdenka; Gavrilin, Eugene; Roivainen, Merja

    2013-01-01

    Vaccine derived poliovirus (VDPV) type 2 strains strongly divergent from the corresponding vaccine strain, Sabin 2, were repeatedly isolated from sewage in Slovakia over a period of 22 months in 2003–2005. Cell cultures of stool specimens from known immune deficient patients and from an identified putative source population of 500 people failed to identify the potential excretor(s) of the virus. The occurrence of VDPV in sewage stopped without any intervention. No paralytic cases were reported in Slovakia during the episode. According to a GenBank search and similarity plotting-analysis, the closest known relative of the first isolate PV2/03/SVK/E783 through all main sections of the genome was the type 2 poliovirus Sabin strain, with nucleotide identities in 5′UTR, P1, P2, P3, and 3′UTR parts of the genome of 88.6, 85.9, 87.3, 88.5, and 94.0 percent, respectively. Phenotypic properties of selected Slovakian aVDPV strains resembled those of VDPV strains isolated from immune deficient individuals with prolonged PV infection (iVDPV), including antigenic changes and moderate neurovirulence in the transgenic mouse model. One hundred and two unique VP1 coding sequences were determined from VDPV strains isolated from 34 sewage specimens. Nucleotide differences from Sabin 2 in the VP1 coding region ranged from 12.5 to 15.6 percent, and reached a maximum of 9.6 percent between the VDPV strains under study. Most of the nucleotide substitutions were synonymous but as many as 93 amino acid positions out of 301 in VP1 showed substitutions. We conclude that (1) individuals with prolonged poliovirus infection are not as rare as suggested by the studies on immune deficient patients known to the health care systems and (2) genetic divergence of VDPV strains may remain extensive during years long replication in humans. PMID:23935826

  19. The Golgi Protein ACBD3, an Interactor for Poliovirus Protein 3A, Modulates Poliovirus Replication

    PubMed Central

    Téoulé, François; Brisac, Cynthia; Pelletier, Isabelle; Vidalain, Pierre-Olivier; Jégouic, Sophie; Mirabelli, Carmen; Bessaud, Maël; Combelas, Nicolas; Autret, Arnaud; Tangy, Frédéric; Delpeyroux, Francis

    2013-01-01

    We have shown that the circulating vaccine-derived polioviruses responsible for poliomyelitis outbreaks in Madagascar have recombinant genomes composed of sequences encoding capsid proteins derived from poliovaccine Sabin, mostly type 2 (PVS2), and sequences encoding nonstructural proteins derived from other human enteroviruses. Interestingly, almost all of these recombinant genomes encode a nonstructural 3A protein related to that of field coxsackievirus A17 (CV-A17) strains. Here, we investigated the repercussions of this exchange, by assessing the role of the 3A proteins of PVS2 and CV-A17 and their putative cellular partners in viral replication. We found that the Golgi protein acyl-coenzyme A binding domain-containing 3 (ACBD3), recently identified as an interactor for the 3A proteins of several picornaviruses, interacts with the 3A proteins of PVS2 and CV-A17 at viral RNA replication sites, in human neuroblastoma cells infected with either PVS2 or a PVS2 recombinant encoding a 3A protein from CV-A17 [PVS2-3A(CV-A17)]. The small interfering RNA-mediated downregulation of ACBD3 significantly increased the growth of both viruses, suggesting that ACBD3 slowed viral replication. This was confirmed with replicons. Furthermore, PVS2-3A(CV-A17) was more resistant to the replication-inhibiting effect of ACBD3 than the PVS2 strain, and the amino acid in position 12 of 3A was involved in modulating the sensitivity of viral replication to ACBD3. Overall, our results indicate that exchanges of nonstructural proteins can modify the relationships between enterovirus recombinants and cellular interactors and may thus be one of the factors favoring their emergence. PMID:23926333

  20. 33 CFR 117.979 - Sabine Lake.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ....979 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS Specific Requirements Texas § 117.979 Sabine Lake. The draw of the S82 bridge, mile 10... signal if at least six hours notice is given to the Maintenance Construction Supervisor or the...

  1. Brunenders: a partially attenuated historic poliovirus type I vaccine strain.

    PubMed

    Sanders, Barbara P; Liu, Ying; Brandjes, Alies; van Hoek, Vladimir; de Los Rios Oakes, Isabel; Lewis, John; Wimmer, Eckard; Custers, Jerome H H V; Schuitemaker, Hanneke; Cello, Jeronimo; Edo-Matas, Diana

    2015-09-01

    Brunenders, a type I poliovirus (PV) strain, was developed in 1952 by J. F. Enders and colleagues through serial in vitro passaging of the parental Brunhilde strain, and was reported to display partial neuroattenuation in monkeys. This phenotype of attenuation encouraged two vaccine manufacturers to adopt Brunenders as the type I component for their inactivated poliovirus vaccines (IPVs) in the 1950s, although today no licensed IPV vaccine contains Brunenders. Here we confirmed, in a transgenic mouse model, the report of Enders on the reduced neurovirulence of Brunenders. Although dramatically neuroattenuated relative to WT PV strains, Brunenders remains more virulent than the attenuated oral vaccine strain, Sabin 1. Importantly, the neuroattenuation of Brunenders does not affect in vitro growth kinetics and in vitro antigenicity, which were similar to those of Mahoney, the conventional type I IPV vaccine strain. We showed, by full nucleotide sequencing, that Brunhilde and Brunenders differ at 31 nucleotides, eight of which lead to amino acid changes, all located in the capsid. Upon exchanging the Brunenders capsid sequence with that of the Mahoney capsid, WT neurovirulence was regained in vivo, suggesting a role for the capsid mutations in Brunenders attenuation. To date, as polio eradication draws closer, the switch to using attenuated strains for IPV is actively being pursued. Brunenders preceded this novel strategy as a partially attenuated IPV strain, accompanied by decades of successful use in the field. Providing data on the attenuation of Brunenders may be of value in the further construction of attenuated PV strains to support the grand pursuit of the global eradication of poliomyelitis.

  2. Identification of an alternative open reading frame ("hidden gene"?) stringently required for infectivity of poliovirus cDNA clones.

    PubMed

    Pierangeli, A; Bucci, M; Forzan, M; Pagnotti, P; Equestre, M; Pérez Bercoff, R

    1998-10-01

    Translation of the uncapped poliovirus RNA starts at the AUG triplet spanning positions 741-743, and proceeds uninterrupted for almost the entire length of the genome. Such a cap-independent mechanism of internal initiation of translation determines that a long, extra-cistronic region extends between the 5'-end and the main open reading frame (ORF). We have identified 10 short ORFs initiated by the alternative translation initiation codons ACG, AUA, and GUG in the 5'-terminal extra-cistronic region (5'-ECR) of poliovirus RNA. Mutations introduced in all but one of these mini-cistrons had no effect on the infectivity of full-length cDNA clones, except when they modified a "hidden frame" spanning between nucleotides 157-192 (starting triplet: ACG). The mini cistron 157-192 is conserved in position, length and sequence in the genome of all types and strains of poliovirus. Adaptation to rat (Lansing) or mouse (variant of Sabin 2) is accompanied by a consistent pattern of changes in the primary sequence of this "hidden frame". The substitutions that abrogated the infectivity of cDNA clones were not expected to modify the predicted secondary structure of the 5'-ECR, and they did not alter the ability of the IRES to direct internal initiation of translation in bi-cistronic mRNAs. The infectivity of the mutated poliovirus cDNAs could be complemented in trans by co-transfecting the target COS-1 cells with an expression vector containing just the 5'-ECR of poliovirus type 2 (Lansing strain). The infectivity of poliovirus cDNA could be restored by co-transfecting short RNA transcripts of the wt 5'-ECR (Lansing), suggesting that the complementation in trans indeed requires the expression of the helper cDNA clone.

  3. Multiple Independent Emergences of Type 2 Vaccine-Derived Polioviruses during a Large Outbreak in Northern Nigeria

    PubMed Central

    Shaw, Jing; Jorba, Jaume; Bukbuk, David; Adu, Festus; Gumede, Nicksy; Pate, Muhammed Ali; Abanida, Emmanuel Ade; Gasasira, Alex; Iber, Jane; Chen, Qi; Vincent, Annelet; Chenoweth, Paul; Henderson, Elizabeth; Wannemuehler, Kathleen; Naeem, Asif; Umami, Rifqiyah Nur; Nishimura, Yorihiro; Shimizu, Hiroyuki; Baba, Marycelin; Adeniji, Adekunle; Williams, A. J.; Kilpatrick, David R.; Oberste, M. Steven; Wassilak, Steven G.; Tomori, Oyewale; Pallansch, Mark A.; Kew, Olen

    2013-01-01

    Since 2005, a large poliomyelitis outbreak associated with type 2 circulating vaccine-derived poliovirus (cVDPV2) has occurred in northern Nigeria, where immunization coverage with trivalent oral poliovirus vaccine (tOPV) has been low. Phylogenetic analysis of P1/capsid region sequences of isolates from each of the 403 cases reported in 2005 to 2011 resolved the outbreak into 23 independent type 2 vaccine-derived poliovirus (VDPV2) emergences, at least 7 of which established circulating lineage groups. Virus from one emergence (lineage group 2005-8; 361 isolates) was estimated to have circulated for over 6 years. The population of the major cVDPV2 lineage group expanded rapidly in early 2009, fell sharply after two tOPV rounds in mid-2009, and gradually expanded again through 2011. The two major determinants of attenuation of the Sabin 2 oral poliovirus vaccine strain (A481 in the 5′-untranslated region [5′-UTR] and VP1-Ile143) had been replaced in all VDPV2 isolates; most A481 5′-UTR replacements occurred by recombination with other enteroviruses. cVDPV2 isolates representing different lineage groups had biological properties indistinguishable from those of wild polioviruses, including efficient growth in neuron-derived HEK293 cells, the capacity to cause paralytic disease in both humans and PVR-Tg21 transgenic mice, loss of the temperature-sensitive phenotype, and the capacity for sustained person-to-person transmission. We estimate from the poliomyelitis case count and the paralytic case-to-infection ratio for type 2 wild poliovirus infections that ∼700,000 cVDPV2 infections have occurred during the outbreak. The detection of multiple concurrent cVDPV2 outbreaks in northern Nigeria highlights the risks of cVDPV emergence accompanying tOPV use at low rates of coverage in developing countries. PMID:23408630

  4. Effect of formaldehyde inactivation on poliovirus.

    PubMed

    Wilton, Thomas; Dunn, Glynis; Eastwood, David; Minor, Philip D; Martin, Javier

    2014-10-01

    Inactivated polio vaccines, which have been used in many countries for more than 50 years, are produced by treating live poliovirus (PV) with formaldehyde. However, the molecular mechanisms underlying virus inactivation are not well understood. Infection by PV is initiated by virus binding to specific cell receptors, which results in viral particles undergoing sequential conformational changes that generate altered structural forms (135S and 80S particles) and leads to virus cell entry. We have analyzed the ability of inactivated PV to bind to the human poliovirus receptor (hPVR) using various techniques such as ultracentrifugation, fluorescence-activated cell sorting flow cytometry and real-time reverse transcription-PCR (RT-PCR). The results showed that although retaining the ability to bind to hPVR, inactivated PV bound less efficiently in comparison to live PV. We also found that inactivated PV showed resistance to structural conversion in vitro, as judged by measuring changes in antigenicity, the ability to bind to hPVR, and viral RNA release at high temperature. Furthermore, viral RNA from inactivated PV was shown to be modified, since cDNA yields obtained by RT-PCR amplification were severely reduced and no infectious virus was recovered after RNA transfection into susceptible cells. Importance: This study represents a novel insight into the molecular mechanisms responsible for poliovirus inactivation. We show that inactivation with formaldehyde has an effect on early steps of viral replication as it reduces the ability of PV to bind to hPVR, decreases the sensitivity of PV to convert to 135S particles, and abolishes the infectivity of its viral RNA. These changes are likely responsible for the loss of infectivity shown by PV following inactivation. Techniques used in this study represent new approaches for the characterization of inactivated PV products and could be useful in developing improved methods for the production and quality control testing of

  5. Effect of Formaldehyde Inactivation on Poliovirus

    PubMed Central

    Dunn, Glynis; Eastwood, David; Minor, Philip D.; Martin, Javier

    2014-01-01

    ABSTRACT Inactivated polio vaccines, which have been used in many countries for more than 50 years, are produced by treating live poliovirus (PV) with formaldehyde. However, the molecular mechanisms underlying virus inactivation are not well understood. Infection by PV is initiated by virus binding to specific cell receptors, which results in viral particles undergoing sequential conformational changes that generate altered structural forms (135S and 80S particles) and leads to virus cell entry. We have analyzed the ability of inactivated PV to bind to the human poliovirus receptor (hPVR) using various techniques such as ultracentrifugation, fluorescence-activated cell sorting flow cytometry and real-time reverse transcription-PCR (RT-PCR). The results showed that although retaining the ability to bind to hPVR, inactivated PV bound less efficiently in comparison to live PV. We also found that inactivated PV showed resistance to structural conversion in vitro, as judged by measuring changes in antigenicity, the ability to bind to hPVR, and viral RNA release at high temperature. Furthermore, viral RNA from inactivated PV was shown to be modified, since cDNA yields obtained by RT-PCR amplification were severely reduced and no infectious virus was recovered after RNA transfection into susceptible cells. IMPORTANCE This study represents a novel insight into the molecular mechanisms responsible for poliovirus inactivation. We show that inactivation with formaldehyde has an effect on early steps of viral replication as it reduces the ability of PV to bind to hPVR, decreases the sensitivity of PV to convert to 135S particles, and abolishes the infectivity of its viral RNA. These changes are likely responsible for the loss of infectivity shown by PV following inactivation. Techniques used in this study represent new approaches for the characterization of inactivated PV products and could be useful in developing improved methods for the production and quality control testing

  6. [Investigation of a Patient with Pre-vaccine-derived Poliovirus in Shandong Province, China].

    PubMed

    Lin, Xiaojuan; Liu, Yao; Wang, Suting; Zhang Xiao; Song, Lizhi; Tao, Zexin; Ji, Feng; Xiong, Ping; Xu, Aiqiang

    2015-09-01

    To analyze the genetic characteristics of a polio-I highly variant vaccine recombinant virus in Shandong Province (China) in 2011 and to identify isolates from healthy contacts, two stool specimens from one patient with acute flaccid paralysis (AFP) and 40 stool specimens from his contacts were collected for virus isolation. The complete genome of poliovirus and VP1 coding region of the non-polio enterovirus were sequenced. Homologous comparison and phylogenetic analyses based on VP1 sequences were undertaken among coxsackievirus (CV) B1, CV-B3 isolates, and those in GenBank. One poliovirus (P1/11186), CV-A4 and CV-A8 were isolated from the AFP patient; one CV-A2, Echovirus 3 (E-3), E-12 and E-14, ten CV-B1, and five CV-B3 strains were isolated from his contacts. These results led us to believe that there may be a human enterovirus epidemic in this area, and that surveillance must be enhanced. P1/11186 was a type-1 vaccine-related poliovirus; it combined with type-2 and type-3 polioviruses in 2A and 3A regions, respectively. There were 25 nucleotide mutations with 9 amino-acid alterations in the entire genome. There were 8 nucleotide mutations with 5 amino-acid alterations in the VP1 region compared with the corresponding Sabin strains. Homology analyses suggested that the ten CV-B1 isolates had 97.0%-100% nucleotide and 98.9%-100% amino-acid identities with each other, as well as 92.6%-100% nucleotide and 99.2%-100% amino-acid identities among the five CV-B3 isolates. Phylogenetic analyses on the complete sequences of VP1 among CV-B1 and CV-B3 isolates showed that Shandong strains, together with strains from other provinces in China, had a close relationship and belonged to the same group.

  7. Standardized Methods for Detection of Poliovirus Antibodies.

    PubMed

    Weldon, William C; Oberste, M Steven; Pallansch, Mark A

    2016-01-01

    Testing for neutralizing antibodies against polioviruses has been an established gold standard for assessing individual protection from disease, population immunity, vaccine efficacy studies, and other vaccine clinical trials. Detecting poliovirus specific IgM and IgA in sera and mucosal specimens has been proposed for evaluating the status of population mucosal immunity. More recently, there has been a renewed interest in using dried blood spot cards as a medium for sample collection to enhance surveillance of poliovirus immunity. Here, we describe the modified poliovirus microneutralization assay, poliovirus capture IgM and IgA ELISA assays, and dried blood spot polio serology procedures for the detection of antibodies against poliovirus serotypes 1, 2, and 3.

  8. Molecular and Phenotypic Characterization of a Highly Evolved Type 2 Vaccine-Derived Poliovirus Isolated from Seawater in Brazil, 2014.

    PubMed

    Cassemiro, Klécia Marília S de Melo; Burlandy, Fernanda M; Barbosa, Mikaela R F; Chen, Qi; Jorba, Jaume; Hachich, Elayse M; Sato, Maria I Z; Burns, Cara C; da Silva, Edson E

    2016-01-01

    A type 2 vaccine-derived poliovirus (VDPV), differing from the Sabin 2 strain at 8.6% (78/903) of VP1 nucleotide positions, was isolated from seawater collected from a seaport in São Paulo State, Brazil. The P1/capsid region is related to the Sabin 2 strain, but sequences within the 5'-untranslated region and downstream of the P1 region were derived from recombination with other members of Human Enterovirus Species C (HEV-C). The two known attenuating mutations had reverted to wild-type (A481G in the 5'-UTR and Ile143Thr in VP1). The VDPV isolate had lost the temperature sensitive phenotype and had accumulated amino acid substitutions in neutralizing antigenic (NAg) sites 3a and 3b. The date of the initiating OPV dose, estimated from the number of synonymous substitutions in the capsid region, was approximately 8.5 years before seawater sampling, a finding consistent with a long time of virus replication and possible transmission among several individuals. Although no closely related type 2 VDPVs were detected in Brazil or elsewhere, this VDPV was found in an area with a mobile population, where conditions may favor both viral infection and spread. Environmental surveillance serves as an important tool for sensitive and early detection of circulating poliovirus in the final stages of global polio eradication.

  9. Effect of substituting IPV for tOPV on immunity to poliovirus in Bangladeshi infants: An open-label randomized controlled trial.

    PubMed

    Mychaleckyj, Josyf C; Haque, Rashidul; Carmolli, Marya; Zhang, Dadong; Colgate, E Ross; Nayak, Uma; Taniuchi, Mami; Dickson, Dorothy; Weldon, William C; Oberste, M Steven; Zaman, K; Houpt, Eric R; Alam, Masud; Kirkpatrick, Beth D; Petri, William A

    2016-01-12

    The Polio Endgame strategy includes phased withdrawal of oral poliovirus vaccines (OPV) coordinated with introduction of inactivated poliovirus vaccine (IPV) to ensure population immunity. The impact of IPV introduction into a primary OPV series of immunizations in a developing country is uncertain. Between May 2011 and November 2012, we enrolled 700 Bangladeshi infant-mother dyads from Dhaka slums into an open-label randomized controlled trial to test whether substituting an injected IPV dose for the standard Expanded Program on Immunization (EPI) fourth tOPV dose at infant age 39 weeks would reduce fecal shedding and enhance systemic immunity. The primary endpoint was mucosal immunity to poliovirus at age one year, measured by fecal excretion of any Sabin virus at five time points up to 25 days post-52 week tOPV challenge, analyzed by the intention to treat principle. We randomized 350 families to the tOPV and IPV vaccination arms. Neither study arm resulted in superior intestinal protection at 52 weeks measured by the prevalence of infants shedding any of three poliovirus serotypes, but the IPV dose induced significantly higher seroprevalence and seroconversion rates. This result was identical for poliovirus detection by cell culture or RT-qPCR. The non-significant estimated culture-based shedding risk difference was -3% favoring IPV, and the two vaccination schedules were inferred to be equivalent within a 95% confidence margin of -10% to +4%. Results for shedding analyses stratified by poliovirus type were similar. Neither of the vaccination regimens is superior to the other in enhancing intestinal immunity as measured by poliovirus shedding at 52 weeks of age and the IPV regimen provides similar intestinal immunity to the four tOPV series, although the IPV regimen strongly enhances humoral immunity. The IPV-modified regimen may be considered for vaccination programs without loss of intestinal protection. Copyright © 2015 The Authors. Published by Elsevier

  10. Cell scientist to watch - Sabine Petry.

    PubMed

    2016-11-15

    Originally from Germany, Sabine Petry received her Diploma (MSc) from Goethe University in Frankfurt and undertook her Master's thesis at the Max Planck Institute of Biophysics. She then moved to the UK to pursue a PhD under the supervision of Venki Ramakrishnan at the MRC Laboratory of Molecular Biology in Cambridge. In 2008, Sabine started her postdoctoral work in the laboratory of Ron Vale at the University of California, San Francisco as an EMBO fellow and then an HHMI postdoctoral fellow of the Life Science Research Foundation. She started her own lab at Princeton University in 2013, and her work has already been recognised with an NIH Pathway to Independence K99/R00 Award and the Kimmel Scholar Award for Cancer Research; she was also named a Pew Scholar and Packard Fellow in 2014. Sabine's research combines structural, biophysical, biochemical and cell biology methods to study the mechanism by which microtubules build cellular structures, allowing cells to attain a particular shape and function. © 2016. Published by The Company of Biologists Ltd.

  11. H1PVAT is a novel and potent early-stage inhibitor of poliovirus replication that targets VP1.

    PubMed

    Tijsma, Aloys; Thibaut, Hendrik Jan; Spieser, Stéphane A H; De Palma, Armando; Koukni, Mohamed; Rhoden, Eric; Oberste, Steve; Pürstinger, Gerhard; Volny-Luraghi, Antonia; Martin, Javier; Marchand, Arnaud; Chaltin, Patrick; Neyts, Johan; Leyssen, Pieter

    2014-10-01

    A novel small molecule, H1PVAT, was identified as a potent and selective inhibitor of the in vitro replication of all three poliovirus serotypes, whereas no activity was observed against other enteroviruses. Time-of-drug-addition studies revealed that the compound interfered with an early stage of virus replication. Four independently-selected H1PVAT-resistant virus variants uniformly carried the single amino acid substitution I194F in the VP1 capsid protein. Poliovirus type 1 strain Sabin, reverse-engineered to contain this substitution, proved to be completely insensitive to the antiviral effect of H1PVAT and was cross-resistant to the capsid-binding inhibitors V-073 and pirodavir. The VP1 I194F mutant had a smaller plaque phenotype than wild-type virus, and the amino acid substitution rendered the virus more susceptible to heat inactivation. Both for the wild-type and VP1 I194F mutant virus, the presence of H1PVAT increased the temperature at which the virus was inactivated, providing evidence that the compound interacts with the viral capsid, and that capsid stabilization and antiviral activity are not necessarily correlated. Molecular modeling suggested that H1PVAT binds with high affinity in the pocket underneath the floor of the canyon that is involved in receptor binding. Introduction of the I194F substitution in the model of VP1 induced a slight concerted rearrangement of the core β-barrel in this pocket, which disfavors binding of the compound. Taken together, the compound scaffold, to which H1PVAT belongs, may represent another promising class of poliovirus capsid-binding inhibitors next to V-073 and pirodavir. Potent antivirals against poliovirus will be essential in the poliovirus eradication end-game.

  12. 75 FR 41119 - Special Local Regulations; Sabine River, Orange, TX

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-15

    ... SECURITY Coast Guard 33 CFR Part 100 RIN 1625-AA08 Special Local Regulations; Sabine River, Orange, TX... River, Orange, Texas. This Special Local Regulation is intended to restrict vessels from portions of the..., testing and race in conjunction with the Orange, TX, Thunder on the Sabine boat races. The powerboat...

  13. 33 CFR 80.840 - Sabine Pass, TX to Galveston, TX.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Sabine Pass, TX to Galveston, TX... INTERNATIONAL NAVIGATION RULES COLREGS DEMARCATION LINES Eighth District § 80.840 Sabine Pass, TX to Galveston, TX. (a) A line drawn from the Sabine Pass East Jetty Light to the seaward end of the Sabine Pass...

  14. 75 FR 74029 - Sabine Pass LNG, L.P.; Notice of Application

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-30

    ... Energy Regulatory Commission Sabine Pass LNG, L.P.; Notice of Application November 22, 2010. Take notice that on November 12, 2010, Sabine Pass LNG, L.P. (Sabine Pass), 700 Milam Street, Suite 800, Houston... a redundant high pressure boil off gas compressor at its existing Sabine Pass LNG Terminal, located...

  15. [Genetic Characteristics of Type 2 Vaccine-derived Poliovirus in Shanxi Province (China) in 2014].

    PubMed

    Yan, Dongrei; Li, Xiaolei; Zhang, Yong; Yang, Jianfang; Zhu, Shuangli; Wang, Dongyan; Zhang, Chuangye; Zhu, Hui; Xu, Wenbo

    2015-03-01

    The World Health Organization redefined the type 2 vaccine-derived poliovirus (VDPV) in 2010. To study the genetic characteristics and evolution of type 2 VDPV under this new definition, we conducted genome sequencing and analyses of type 2 VDPVs isolated from one patient with acute flaccid paralysis in Shanxi province (China) in 2014. Nucleotide sequencing revealed that the full-length of type 2 VDPV is 7439 bases encoding 2207 amino acids with no insertion or deletion of nucleotides compared with Sabin2. One nucleotide substitution identified as a key determinant of the attenuated phenotype of the Sabin 2 strain (A-G reversion at nucleotide nt 481 in the 5-end of the untranslated region) had reverted in the Shanxi type 2 VDPV. The other known key determinant of the attenuated phenotype of the Sabin 2 strain (U-->C reversion at nt2909 in the VP1 coding region that caused a Ile143Thr substitution in VP1) had not reverted in the Shanxi VDPV. The Shanxi type 2 VDPV was S2/S1 recombinant, the crossover site of which mapped to the 3-end of the 3D region (between nt 6247 and nt 6281). A phylogentic tree based on the VP1 coding region showed that evolution of the Shanxi type 2 VDPV was independent of other type 2 VDPVs detected worldwide. We estimated that the strain circulated for approximately = 11 months in the population according to the known evolution rate. The present study confirmed that the Chinese Polio Laboratory Network could discover the VDPV promptly and that it played an important part in maintenance of a polio-free China.

  16. Long-Term Circulation of Vaccine-Derived Poliovirus That Causes Paralytic Disease

    PubMed Central

    Cherkasova, Elena A.; Korotkova, Ekaterina A.; Yakovenko, Maria L.; Ivanova, Olga E.; Eremeeva, Tatyana P.; Chumakov, Konstantin M.; Agol, Vadim I.

    2002-01-01

    Successful implementation of the global poliomyelitis eradication program raises the problem of vaccination against poliomyelitis in the posteradication era. One of the options under consideration envisions completely stopping worldwide the use of the Sabin vaccine. This strategy is based on the assumption that the natural circulation of attenuated strains and their derivatives is strictly limited. Here, we report the characterization of a highly evolved derivative of the Sabin vaccine strain isolated in a case of paralytic poliomyelitis from a 7-month-old immunocompetent baby in an apparently adequately immunized population. Analysis of the genome of this isolate showed that it is a double (type 1-type 2-type 1) vaccine-derived recombinant. The number of mutations accumulated in both the type 1-derived and type 2-derived portions of the recombinant genome suggests that both had diverged from their vaccine predecessors ∼2 years before the onset of the illness. This fact, along with other recent observations, points to the possibility of long-term circulation of Sabin vaccine strain derivatives associated with an increase in their neurovirulence. Comparison of genomic sequences of this and other evolved vaccine-derived isolates reveals some general features of natural poliovirus evolution. They include a very high preponderance and nonrandom distribution of synonymous substitutions, conservation of secondary structures of important cis-acting elements of the genome, and an apparently adaptive character of most of the amino acid mutations, with only a few of them occurring in the antigenic determinants. Another interesting feature is a frequent occurrence of tripartite intertypic recombinants with either type 1 or type 3 homotypic genomic ends. PMID:12050392

  17. 78 FR 79434 - Sabine River Authority of Texas and Sabine River Authority, State of Louisiana; Notice of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-30

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Sabine River Authority of Texas and Sabine River Authority, State of Louisiana; Notice of Availability of the Final Environmental Impact Statement for the Toledo Bend Hydroelectric Project In accordance with the...

  18. Water resources of Sabine Parish, Louisiana

    USGS Publications Warehouse

    Prakken, Lawrence B.; White, Vincent E.; Lovelace, John K.

    2014-01-01

    Information concerning the availability, use, and quality of water in Sabine Parish, Louisiana, is critical for proper water-supply management. The purpose of this fact sheet is to present information that can be used by water managers, parish residents, and others for stewardship of this vital resource. Information on the availability, past and current use, use trends, and water quality from groundwater and surface-water sources in the parish is presented. Previously published reports and data stored in the U.S. Geological Survey’s (USGS) National Water Information System (http://waterdata.usgs.gov/nwis) are the primary sources of the information presented here.

  19. Inactivation of poliovirus by formaldehyde

    PubMed Central

    Gard, Sven

    1957-01-01

    Since formaldehyde, either alone or in combination with other inactivating agents, is at present used in the production of all so-called “killed” poliovirus vaccines, a thorough knowledge of the kinetics of the reaction between the chemical agent and the virus, and of the mechanisms involved, is of great practical importance. In this paper the problem is discussed against the background of present knowledge of the structure of the virus and the chemical nature of the action of formaldehyde. PMID:13511143

  20. Evolution and circulation of type-2 vaccine-derived polioviruses in Nad Ali district of Southern Afghanistan during June 2009-February 2011.

    PubMed

    Sharif, Salmaan; Abbasi, Bilal Haider; Khurshid, Adnan; Alam, Muhammad Masroor; Shaukat, Shahzad; Angez, Mehar; Rana, Muhammad Suleman; Zaidi, Syed Sohail Zahoor

    2014-01-01

    Oral polio vaccine has been used successfully as a powerful tool to control the spread of wild polioviruses throughout the world; however, during replication in under immunized children, some vaccine viruses revert and acquire the neurovirulent phenotypic properties. In this study, we describe the evolution and circulation of Vaccine-Derived Polioviruses (VDPVs) in Helmand province of Afghanistan. We investigated 2646 AFP cases of Afghan children from June 2009-February 2011 and isolated 103 (04%) vaccine viruses, 45(1.7%) wild type polioviruses and six (0.22%) type 2 circulating vaccine-derived polioviruses (cVDPVs). These cVDPVs showed 97.7%-98.2% nucleotide and 98%-98.7% amino acid homology in VP1 region on comparison with Sabin type 2 reference strain. All these cVDPVs had two signature mutations of neurovirulent phenotypes and 12 additional mutations in P1 capsid region that might also have contributed to increase neurovirulence and replication. Phylogenetic analysis revealed that all these viruses were closely related and originated from previously reported Sabin like 2 virus from Pakistan which did not conform to the standard definition of VDPVs at that time. It was also observed that initial OPV dose was administered approximately 9 months prior to the collection of first stool specimen of index case. Our findings support that suboptimal surveillance and low routine immunization coverage have contributed to the emergence and spread of these viruses in Afghanistan. We therefore recommend high quality immunization campaigns not only in affected district Nad Ali but also in the bordering areas between Pakistan and Afghanistan to prevent the spread of cVDPVs.

  1. [Role of the National Poliovirus Laboratory for the Program of eradication and poliomyelitis surveillance].

    PubMed

    Trallero, Gloria; Cabrerizo, María; Avellón, Ana

    2013-01-01

    The Spanish acute flaccid paralysis surveillance network is coordinated by the National Poliovirus Laboratory (NPL), which, since 1998, carries out polioviruses (PV) and other enteroviruses detected characterization by cell culture and molecular techniques. A total of 110,725 (70046+40679) samples were studied between 1998-2012 and enteroviruses were detected in 8% of these. Among these enteroviruses 241 PV were characterized as PV Sabin-like, except samples belong to an imported poliomyelitis case, all of which were characterised as vaccine derived PV type 2. The NPL has carried out the serotyping and the intratypic differentiation of all the isolated PV in Spain of any syndrome. It is shown that wild PV has not circulated in our country during the 15 years studied and that has led to the signing of the Act of the "eradication of poliomyelitis in Spain" by WHO in 2001, and the /"certification of the eradication of wild PV free for European countries" on 21 June 2002. Currently only 3 countries have endemic transmission of wild PV (Pakistan, Afghanistan and Nigeria). Until a complete worldwide eradication, was achieved, Spain will actively continue to participate in the maintenance of the poliomyelitis eradication infrastructure by monitoring and vaccination as well as the wild PV containment plan to avoid the spread of wild PV.

  2. Genotype-specific RNA probes for direct identification of wild polioviruses by blot hybridization.

    PubMed Central

    De, L; Yang, C F; Da Silva, E; Boshell, J; Cáceres, P; Gómez, J R; Pallansch, M; Kew, O

    1997-01-01

    We have developed RNA probes for the direct identification of wild poliovirus isolates by blot hybridization. The probes are complementary to sequences of the first 30 to 32 codons of VP1, which evolve more extensively (approximately 1.5-fold) than the rest of VP1. To illustrate our general approach, we describe the design of probes specific to each of four major genotypes recently endemic (1981 to 1991) to the Americas: Andean type 1, Brazil type 1, Brazil type 3, and Central America-Mexico type 3. A wild isolate of each genotype was selected according to molecular and epidemiologic criteria to be representative of the principal lineages in circulation. Variable VP1 sequences of the representative isolates were amplified by the reverse transcriptase PCR and were inserted into a plasmid vector containing a T7 promoter. The in vitro transcripts, labeled with digoxigenin, served as probes. These formed stable hybrids only with RNAs of isolates of the corresponding genotypes. Hybrids were detected by a sensitive chemiluminescence assay, capable under normal diagnostic conditions of detecting specific wild poliovirus sequences in samples containing up to a 100-fold excess of Sabin vaccine strain-related sequences of the same serotype. PMID:9350743

  3. Functional domains of the poliovirus receptor

    SciTech Connect

    Koike, Satoshi; Ise, Iku; Nomoto, Akio )

    1991-05-15

    A number of mutant cDNAs of the human poliovirus receptor were constructed to identify essential regions of the molecule as the receptor. All mutant cDNAs carrying the sequence coding for the entire N-terminal immunoglobulin-like domain (domain I) confer permissiveness for poliovirus to mouse L cells, but a mutant cDNA lacking the sequence for domain I does not. The transformants permissive for poliovirus were able to bind the virus and were also recognized by monoclonal antibody D171, which competes with poliovirus for the cellular receptor. These results strongly suggest that the poliovirus binding site resides in domain I of the receptor. Mutant cDNAs for the sequence encoding the intracellular peptide were also constructed and expressed in mouse L cells. Susceptibility of these cells to poliovirus revealed that the entire putative cytoplasmic domain is not essential for virus infection. Thus, the cytoplasmic domain of the molecule appears not to play a role in the penetration of poliovirus.

  4. In vitro replication of poliovirus

    SciTech Connect

    Lubinski, J.M.

    1986-01-01

    Poliovirus is a member of the Picornaviridae whose genome is a single stranded RNA molecule of positive polarity surrounded by a proteinaceous capsid. Replication of poliovirus occurs via negative strand intermediates in infected cells using a virally encoded RNA-dependent RNA polymerase and host cell proteins. The authors have exploited the fact that complete cDNA copies of the viral genome when transfected onto susceptible cells generate virus. Utilizing the bacteriophage SP6 DNA dependent RNA polymerase system to synthesize negative strands in vitro and using these in an in vitro reaction the authors have generated full length infectious plus strands. Mutagenesis of the 5' and 3' ends of the negative and positive strands demonstrated that replication could occur either de novo or be extensions of the templates from their 3' ends or from nicks occurring during replication. The appearance of dimeric RNA molecules generated in these reactions was not dependent upon the same protein required for de novo initiation. Full length dimeric RNA molecules using a 5' /sup 32/P end-labelled oligo uridylic acid primer and positive strand template were demonstrated in vitro containing only the 35,000 Mr host protein and the viral RNA-dependent RNA polymerase. A model for generating positive strands without protein priming by cleavage of dimeric RNA molecules was proposed.

  5. Antibody responses of Macaca fascicularis against a new inactivated polio vaccine derived from Sabin strains (sIPV) in DTaP-sIPV vaccine.

    PubMed

    Sato, Y; Shiosaki, K; Goto, Y; Sonoda, K; Kino, Y

    2013-05-01

    Antibody responses of Macaca fascicularis against a new tetravalent vaccine composed of diphtheria toxoid, tetanus toxoid, acellular pertussis antigens, and inactivated poliovirus derived from Sabin strains (sIPV) was investigated to predict an optimal dose of sIPV in a new tetravalent vaccine (DTaP-sIPV) prior to conducting a dose-defined clinical study. Monkeys were inoculated with DTaP-sIPVs containing three different antigen units of sIPVs: Vaccine A (types 1:2:3 = 3:100:100 DU), Vaccine B (types 1:2:3 = 1.5:50:50 DU), and Vaccine C (types 1:2:3 = 0.75:25:25 DU). There was no difference in the average titers of neutralizing antibody against the attenuated or virulent polioviruses between Vaccines A and B. The average neutralizing antibody titers of Vaccine C tended to be lower than those of Vaccines A and B. The sIPV antigens did not affect the anti-diphtheria or anti-tetanus antibody titers of DTaP-sIPV. Furthermore, the average neutralizing antibody titers of Vaccine A against the attenuated and virulent polioviruses were comparable between M. fascicularis and humans. These results suggest that M. fascicularis may be a useful animal model for predicting the antibody responses to sIPVs in humans, and that it may be likely to reduce the amount of sIPVs contained in DTaP-sIPVs, even for humans.

  6. Development of Plaque Assay Systems for Poliovirus.

    DTIC Science & Technology

    1982-04-01

    from as little as 25 mg/mL (1/10th of that used in the actual plaque assay) to 1000 mg/mL, and to inhibit poliovirus cytopathic effect In...1067 DEVELOPMENT OF PLAQUE ASSAY SYSTEMS FOR POLIOVIRUS (U) by R.E. Fulton and K. Munroe Abstract During the summer months of 1978, Ms. Krista Munroe...quantitation of infectious poliovirus type 1. .Two different plaque assay techniques were developed and compared. The results of this work are presented

  7. Community transmission of type 2 poliovirus after cessation of trivalent oral polio vaccine in Bangladesh: an open-label cluster-randomised trial and modelling study.

    PubMed

    Taniuchi, Mami; Famulare, Michael; Zaman, Khalequ; Uddin, Md Jashim; Upfill-Brown, Alexander M; Ahmed, Tahmina; Saha, Parimalendu; Haque, Rashidul; Bandyopadhyay, Ananda S; Modlin, John F; Platts-Mills, James A; Houpt, Eric R; Yunus, Mohammed; Petri, William A

    2017-07-07

    Trivalent oral polio vaccine (tOPV) was replaced worldwide from April, 2016, by bivalent types 1 and 3 oral polio vaccine (bOPV) and one dose of inactivated polio vaccine (IPV) where available. The risk of transmission of type 2 poliovirus or Sabin 2 virus on re-introduction or resurgence of type 2 poliovirus after this switch is not understood completely. We aimed to assess the risk of Sabin 2 transmission after a polio vaccination campaign with a monovalent type 2 oral polio vaccine (mOPV2). We did an open-label cluster-randomised trial in villages in the Matlab region of Bangladesh. We randomly allocated villages (clusters) to either: tOPV at age 6 weeks, 10 weeks, and 14 weeks; or bOPV at age 6 weeks, 10 weeks, and 14 weeks and either one dose of IPV at age 14 weeks or two doses of IPV at age 14 weeks and 18 weeks. After completion of enrolment, we implemented an mOPV2 vaccination campaign that targeted 40% of children younger than 5 years, regardless of enrolment status. The primary outcome was Sabin 2 incidence in the 10 weeks after the campaign in per-protocol infants who did not receive mOPV2, as assessed by faecal shedding of Sabin 2 by reverse transcriptase quantitative PCR (RT-qPCR). The effect of previous immunity on incidence was also investigated with a dynamical model of poliovirus transmission to observe prevalence and incidence of Sabin 2 virus. This trial is registered at ClinicalTrials.gov, number NCT02477046. Between April 30, 2015, and Jan 14, 2016, individuals from 67 villages were enrolled to the study. 22 villages (300 infants) were randomly assigned tOPV, 23 villages (310 infants) were allocated bOPV and one dose of IPV, and 22 villages (329 infants) were assigned bOPV and two doses of IPV. Faecal shedding of Sabin 2 in infants who did not receive the mOPV2 challenge did not differ between children immunised with bOPV and one or two doses of IPV and those who received tOPV (15 of 252 [6%] vs six of 122 [4%]; odds ratio [OR] 1·29, 95% CI 0

  8. Public health response to the silent reintroduction of wild poliovirus to Israel, 2013-2014.

    PubMed

    Moran-Gilad, J; Kaliner, E; Gdalevich, M; Grotto, I

    2016-12-01

    During 2013/14, Israel witnessed the silent reintroduction and sustained transmission of wild poliovirus type 1 (WPV1) detected through routine environmental surveillance performed on sewage samples. The public health response to silent poliovirus transmission in a population with high inactivated polio vaccine (IPV) coverage poses an emerging challenge towards the 'End Game' of global poliovirus eradication. This paper reviews the risk assessment, risk management and risk communication aspects of this poliovirus incident. Special emphasis is placed on the use of scientific data generated in the risk assessment phase to inform the public health response. Reintroducing a live vaccine in supplemental immunization activities in response to transmission of WPV or vaccine-derived poliovirus should be considered close to the 'End Game' of polio eradication, especially if targeting the population at risk is feasible. Such circumstances require a comprehensive contingency plan that will support the generation of important public health evidence at the risk assessment stage, thereby allowing to tailor the risk management approaches and underpin appropriate risk communication.

  9. New Generation of Inactivated Poliovirus Vaccines for Universal Immunization After Eradication of Poliomyelitis

    PubMed Central

    Chumakov, Konstantin; Ehrenfeld, Ellie

    2008-01-01

    Twenty years of global polio eradication efforts may soon eliminate wild-type poliovirus transmission. However, new information about poliovirus learned during this campaign, as well as the political realities of a modern world demand that universal immunity against poliomyelitis be maintained even after wild poliovirus is eradicated. Although two excellent vaccines have proven highly effective in the past, neither the live nor current inactivated products are optimal for use in the post-eradication setting. Therefore, concerted efforts are urgently needed to develop a new generation of vaccine that is risk-free and affordable and can be produced on a global scale. Here we discuss the desired properties and ways to create a new polio vaccine. PMID:18990066

  10. Outbreak of type 1 wild poliovirus infection in adults, Namibia, 2006.

    PubMed

    Yusuf, Nasir; de Wee, Rosalina; Foster, Norbert; Watkins, Margaret A; Tiruneh, Desta; Chauvin, Claire; Bossarte, Robert; Mandlhate, Custodia; Jack, Abdoulie; Gumede, Nicksy; Mawela, Alfred; Burns, Cara C; Pallansch, Mark A; Allies, Tina; Rainey, Jeannette; Mataruse, Noah; Nshimirimana, Deo

    2014-11-01

    A paralytic poliomyelitis outbreak occurred in Namibia in 2006, almost exclusively among adults. Nineteen cases were virologically confirmed as due to wild poliovirus type 1 (WPV1), and 26 were classified as polio compatible. Eleven deaths occurred among confirmed and compatible cases (24%). Of the confirmed cases, 97% were aged 15-45 years, 89% were male, and 71% lived in settlement areas in Windhoek. The virus was genetically related to a virus detected in 2005 in Angola, which had been imported earlier from India. The outbreak is likely due to immunity gaps among adults who were inadequately vaccinated during childhood. This outbreak underscores the ongoing risks posed by poliovirus importations, the importance of maintaining strong acute flaccid paralysis surveillance even in adults, and the need to maintain high population immunity to avoid polio outbreaks in the preeradication period and outbreaks due to vaccine-derived polioviruses in the posteradication era.

  11. Will containment of wild poliovirus in laboratories and inactivated poliovirus vaccine production sites be effective for global certification?

    PubMed Central

    Dowdle, Walter R.; Wolff, Christopher; Sanders, Raymond; Lambert, Scott; Best, Maureen

    2004-01-01

    The absolute laboratory containment of any virus cannot be guaranteed, but a wealth of experience indicates that effective containment of wild poliovirus materials for global certification is technically and operationally feasible. Effective containment is based on the principles of minimal wild poliovirus infectious and potentially infectious materials in laboratories; minimal risks of operations in laboratories and inactivated poliovirus vaccine production facilities; minimal susceptibility of workers to wild poliovirus infection and shedding; and minimal susceptibility of populations to wild poliovirus spread. Each principle alone is imperfect, but collectively they greatly minimize the risks of transmitting wild poliovirus from the laboratory to the community. PMID:15106302

  12. The potential benefits of a new poliovirus vaccine for long-term poliovirus risk management.

    PubMed

    Duintjer Tebbens, Radboud J; Thompson, Kimberly M

    2016-12-01

    To estimate the incremental net benefits (INBs) of a hypothetical ideal vaccine with all of the advantages and no disadvantages of existing oral and inactivated poliovirus vaccines compared with current vaccines available for future outbreak response. INB estimates based on expected costs and polio cases from an existing global model of long-term poliovirus risk management. Excluding the development costs, an ideal poliovirus vaccine could offer expected INBs of US$1.6 billion. The ideal vaccine yields small benefits in most realizations of long-term risks, but great benefits in low-probability-high-consequence realizations. New poliovirus vaccines may offer valuable insurance against long-term poliovirus risks and new vaccine development efforts should continue as the world gathers more evidence about polio endgame risks.

  13. Identification and Manipulation of the Molecular Determinants Influencing Poliovirus Recombination

    PubMed Central

    Runckel, Charles; Westesson, Oscar; Andino, Raul; DeRisi, Joseph L.

    2013-01-01

    The control and prevention of communicable disease is directly impacted by the genetic mutability of the underlying etiological agents. In the case of RNA viruses, genetic recombination may impact public health by facilitating the generation of new viral strains with altered phenotypes and by compromising the genetic stability of live attenuated vaccines. The landscape of homologous recombination within a given RNA viral genome is thought to be influenced by several factors; however, a complete understanding of the genetic determinants of recombination is lacking. Here, we utilize gene synthesis and deep sequencing to create a detailed recombination map of the poliovirus 1 coding region. We identified over 50 thousand breakpoints throughout the genome, and we show the majority of breakpoints to be concentrated in a small number of specific “hotspots,” including those associated with known or predicted RNA secondary structures. Nucleotide base composition was also found to be associated with recombination frequency, suggesting that recombination is modulated across the genome by predictable and alterable motifs. We tested the predictive utility of the nucleotide base composition association by generating an artificial hotspot in the poliovirus genome. Our results imply that modification of these motifs could be extended to whole genome re-designs for the development of recombination-deficient, genetically stable live vaccine strains. PMID:23408891

  14. Complementation of a poliovirus defective genome by a recombinant vaccinia virus which provides poliovirus P1 capsid precursor in trans.

    PubMed Central

    Ansardi, D C; Porter, D C; Morrow, C D

    1993-01-01

    Defective interfering (DI) RNA genomes of poliovirus which contain in-frame deletions in the P1 capsid protein-encoding region have been described. DI genomes are capable of replication and can be encapsidated by capsid proteins provided in trans from wild-type poliovirus. In this report, we demonstrate that a previously described poliovirus DI genome (K. Hagino-Yamagishi and A. Nomoto, J. Virol. 63:5386-5392, 1989) can be complemented by a recombinant vaccinia virus, VVP1 (D. C. Ansardi, D. C. Porter, and C. D. Morrow, J. Virol. 65:2088-2092, 1991), which expresses the poliovirus capsid precursor polyprotein, P1. Stocks of defective polioviruses were generated by transfecting in vitro-transcribed defective genome RNA derived from plasmid pSM1(T7)1 into HeLa cells infected with VVP1 and were maintained by serial passage in the presence of VVP1. Encapsidation of the defective poliovirus genome was demonstrated by characterizing poliovirus-specific protein expression in cells infected with preparations of defective poliovirus and by Northern (RNA) blot analysis of poliovirus-specific RNA incorporated into defective poliovirus particles. Cells infected with preparations of defective poliovirus expressed poliovirus protein 3CD but did not express capsid proteins derived from a full-length P1 precursor. Poliovirus-specific RNA encapsidated in viral particles generated in cells coinfected with VVP1 and defective poliovirus migrated slightly faster on formaldehyde-agarose gels than wild-type poliovirus RNA, demonstrating maintenance of the genomic deletion. By metabolic radiolabeling with [35S]methionine-cysteine, the defective poliovirus particles were shown to contain appropriate mature-virion proteins. This is the first report of the generation of a pure population of defective polioviruses free of contaminating wild-type poliovirus. We demonstrate the use of this recombinant vaccinia virus-defective poliovirus genome complementation system for studying the effects of

  15. 75 FR 33803 - Sabine Pipe Line LLC; Notice of Request Under Blanket Authorization

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-15

    ... Energy Regulatory Commission Sabine Pipe Line LLC; Notice of Request Under Blanket Authorization June 8, 2010. Take notice that on June 1, 2010, Sabine Pipe Line LLC (Sabine), 4800 Fournace Place, Bellaire... L. Kirk, Regulatory Specialist, Chevron Pipe Line Company, 4800 Fournace Place, Bellaire, Texas...

  16. Mapping of attenuating sequences of an avirulent poliovirus type 2 strain.

    PubMed

    Moss, E G; O'Neill, R E; Racaniello, V R

    1989-05-01

    A mouse model for poliomyelitis was used to identify genomic sequences that attenuate neurovirulence of poliovirus strain P2/P712. This type 2 strain is avirulent in primates and mice yet grows as well as virulent strains in cell culture. The approach used was to exchange portions of the genome of the mouse-virulent P2/Lansing strain with the corresponding region from P2/P712 to identify sequences that could attenuate Lansing neurovirulence in mice. A full-length infectious cDNA of P2/P712 was assembled and used to construct recombinants between P2/P712 and P2/Lansing. The results of neurovirulence testing of 11 recombinants indicated that strong attenuating determinants are located in the 5' noncoding region of P2/P712 and a region encoding capsid protein VP1 and 2Apro, 2B, and part of 2C. An attenuating determinant was further localized to between nucleotides 456 and 628 of P2/P712. A third sequence from P2/P712, nucleotides 752 to 2268, encoding VP4, VP2, and part of VP3, was weakly attenuating. The sequence from nucleotide 4454, approximately halfway through the 2C-coding region, to the end of the P2/P712 genome did not contain attenuating determinants. Nucleotide sequence analysis revealed that P2/P712 differs from the type 2 Sabin vaccine strain by only 22 nucleotides. Six differences lead to amino acid changes in the coding region, and four differences are in the 5' noncoding region. These studies show that, like the type 1 and type 3 Sabin vaccine strains, the attenuated type 2 strain P712 contains multiple attenuating sequences, including strongly attenuating sequences in the 5' noncoding region of the genome.

  17. Poliovirus Adsorption by 34 Minerals and Soils

    PubMed Central

    Moore, Rebecca S.; Taylor, Dene H.; Sturman, Lawrence S.; Reddy, Michael M.; Fuhs, G. Wolfgang

    1981-01-01

    The adsorption of radiolabeled infectious poliovirus type 2 by 34 well-defined soils and mineral substrates was analyzed in a synthetic freshwater medium containing 1 mM CaCl2 and 1.25 mM NaHCO3 at pH 7. In a model system, adsorption of poliovirus by Ottawa sand was rapid and reached equilibrium within 1 h at 4°C. Near saturation, the adsorption could be described by the Langmuir equation; the apparent surface saturation was 2.5 × 106 plaque-forming units of poliovirus per mg of Ottawa sand. At low surface coverage, adsorption was described by the Freundlich equation. The soils and minerals used ranged from acidic to basic and from high in organic content to organic free. The available negative surface charge on each substrate was measured by the adsorption of a cationic polyelectrolyte, polydiallyldimethylammonium chloride. Most of the substrates adsorbed more than 95% of the virus. In general, soils, in comparison with minerals, were weak adsorbents. Among the soils, muck and Genesee silt loam were the poorest adsorbents; among the minerals, montmorillonite, glauconite, and bituminous shale were the least effective. The most effective adsorbents were magnetite sand and hematite, which are predominantly oxides of iron. Correlation coefficients for substrate properties and virus adsorption revealed that the elemental composition of the adsorbents had little effect on poliovirus uptake. Substrate surface area and pH, by themselves, were not significantly correlated with poliovirus uptake. A strong negative correlation was found between poliovirus adsorption and both the contents of organic matter and the available negative surface charge on the substrates as determined by their capacities for adsorbing the cationic polyelectrolyte, polydiallyldimethylammonium chloride. PMID:6274259

  18. Update on Vaccine-Derived Polioviruses - Worldwide, January 2015-May 2016.

    PubMed

    Jorba, Jaume; Diop, Ousmane M; Iber, Jane; Sutter, Roland W; Wassilak, Steven G; Burns, Cara C

    2016-08-05

    In 1988, the World Health Assembly resolved to eradicate poliomyelitis worldwide (1). One of the main tools used in polio eradication efforts has been the live, attenuated, oral poliovirus vaccine (OPV) (2), an inexpensive vaccine easily administered by trained volunteers. OPV might require several doses to induce immunity, but provides long-term protection against paralytic disease. Through effective use of OPV, the Global Polio Eradication Initiative (GPEI) has brought wild polioviruses to the threshold of eradication (1). However, OPV use, particularly in areas with low routine vaccination coverage, is associated with the emergence of genetically divergent vaccine-derived polioviruses (VDPVs) whose genetic drift from the parental OPV strains indicates prolonged replication or circulation (3). VDPVs can emerge among immunologically normal vaccine recipients and their contacts as well as among persons with primary immunodeficiencies (PIDs). Immunodeficiency-associated VDPVs (iVDPVs) can replicate for years in some persons with PIDs. In addition, circulating vaccine-derived polioviruses (cVDPVs) (3) can emerge in areas with low OPV coverage and can cause outbreaks of paralytic polio. This report updates previous summaries regarding VDPVs (4).

  19. [Eradication of poliomyelitis and emergence of pathogenic vaccine-derived polioviruses: from Madagascar to Cameroon].

    PubMed

    Delpeyroux, Francis; Colbère-Garapin, Florence; Razafindratsimandresy, Richter; Sadeuh-Mba, Serge; Joffret, Marie-Line; Rousset, Dominique; Blondel, Bruno

    2013-11-01

    The oral poliovaccine, a live vaccine made of attenuated poliovirus strains, is the main tool of the vaccination campaigns organised for eradicating poliomyelitis. these campaigns had led to the decline and, thereafter, to the disappearance of wild poliovirus strains of the three serotypes (1-3) in most parts of the world. However, when the poliovaccine coverage becomes too low, vaccine polioviruses can circulate in insufficiently immunized populations and become then pathogenic by mutations and genetic recombination with other enteroviruses of the same species, in particular some coxsackievirus A. These mutated and recombinant vaccine strains have been implicated in several epidemics of paralytic poliomyelitis. Two polio outbreaks associated with these pathogenic circulating vaccine-derived poliovirus (cVDPV) occurred in 2001-2002 and 2005 in the South of Madagascar where vaccine coverage was low. These cVDPV, of serotype 2 or 3, were isolated from paralyzed children and some of their healthy contacts. Other cVDPV were isolated in the same region from healthy children in 2011, indicating that these viruses were circulating again. Vaccination campaigns could stop the outbreaks in 2002 and 2005, and most probably prevent another one in 2011. Therefore, the genetic plasticity of poliovaccine strains that threatens the benefit of vaccination campaigns is the target of an accurate surveillance and an important theme of studies in the virology laboratories of the Institut Pasteur international network.

  20. Poliovirus Laboratory Based Surveillance: An Overview.

    PubMed

    Zaidi, Syed Sohail Zahoor; Asghar, Humayun; Sharif, Salmaan; Alam, Muhammad Masroor

    2016-01-01

    World Health Assembly (WHA) in 1988 encouraged the member states to launch Global Polio Eradication Initiative (GPEI) (resolution WHA41.28) against "the Crippler" called poliovirus, through strong routine immunization program and intensified surveillance systems. Since its launch, global incidence of poliomyelitis has been reduced by more than 99 % and the disease squeezed to only three endemic countries (Afghanistan, Pakistan, and Nigeria) out of 125. Today, poliomyelitis is on the verge of eradication, and their etiological agents, the three poliovirus serotypes, are on the brink of extinction from the natural environment. The last case of poliomyelitis due to wild type 2 strain occurred in 1999 in Uttar Pradesh, India whereas the last paralytic case due to wild poliovirus type 3 (WPV3) was seen in November, 2012 in Yobe, Nigeria. Despite this progress, undetected circulation cannot fully rule out the eradication as most of the poliovirus infections are entirely subclinical; hence sophisticated environmental surveillance is needed to ensure the complete eradication of virus. Moreover, the vaccine virus in under-immunized communities can sometimes revert and attain wild type characteristics posing a big challenge to the program.

  1. The poliovirus 135S particle is infectious.

    PubMed Central

    Curry, S; Chow, M; Hogle, J M

    1996-01-01

    The molecular mechanism of cell entry by unenveloped viruses is poorly understood. The picornaviruses poliovirus, human rhinovirus, and coxsackievirus convert to an altered form (the 135S or A particle) upon interaction with receptors on susceptible cells at 37 degrees C. The 135S particle is thought to be a necessary intermediate because it accumulates inside susceptible cells soon after infection and drugs which inhibit conversion of the virus to this form also prevent infection. However, since a variable fraction of the altered 135S particles is reported to elute unproductively from the surface of susceptible cells, their precise role remains unclear. We have found that poliovirus 135S particles can infect Chinese hamster ovary (CHO) and murine L cells, neither of which are susceptible to infection by native poliovirus. The infectivity of the particles in tissue culture appears to be between 10(3) to 10(5) times less than that of poliovirus on HeLa cells. The 135S particle infectivity was not sensitive to RNase but was greatly reduced by proteolytic treatment. Proteolysis specifically removed the newly exposed N terminus of VP1, a feature which has previously been shown to mediate interactions of the particle with lipid membranes. These results demonstrate that although the infectivity of the 135S particle appears to be receptor independent, it nonetheless requires some property associated with the protein coat. In particular, the N terminus of VP1 plays an important role in the infection process. Our findings are consistent with the hypothesis that the 135S particle is an intermediate in the normal cell entry pathway of poliovirus infection. PMID:8794359

  2. Has Wild Poliovirus Been Eliminated from Nigeria?

    PubMed

    Famulare, Michael

    2015-01-01

    Wild poliovirus type 3 (WPV3) has not been seen anywhere since the last case of WPV3-associated paralysis in Nigeria in November 2012. At the time of writing, the most recent case of wild poliovirus type 1 (WPV1) in Nigeria occurred in July 2014, and WPV1 has not been seen in Africa since a case in Somalia in August 2014. No cases associated with circulating vaccine-derived type 2 poliovirus (cVDPV2) have been detected in Nigeria since November 2014. Has WPV1 been eliminated from Africa? Has WPV3 been eradicated globally? Has Nigeria interrupted cVDPV2 transmission? These questions are difficult because polio surveillance is based on paralysis and paralysis only occurs in a small fraction of infections. This report provides estimates for the probabilities of poliovirus elimination in Nigeria given available data as of March 31, 2015. It is based on a model of disease transmission that is built from historical polio incidence rates and is designed to represent the uncertainties in transmission dynamics and poliovirus detection that are fundamental to interpreting long time periods without cases. The model estimates that, as of March 31, 2015, the probability of WPV1 elimination in Nigeria is 84%, and that if WPV1 has not been eliminated, a new case will be detected with 99% probability by the end of 2015. The probability of WPV3 elimination (and thus global eradication) is > 99%. However, it is unlikely that the ongoing transmission of cVDPV2 has been interrupted; the probability of cVDPV2 elimination rises to 83% if no new cases are detected by April 2016.

  3. Sabin Special Education. A Model To Model: Collaborate To Integrate.

    ERIC Educational Resources Information Center

    Colorado Springs Public Schools, CO.

    This collection of materials presents guidelines and forms used in the Sabin Junior High School (Colorado Springs, Colorado) special education collaborative program. A flow chart illustrates the continuum of services offered by the model. Contents of the manual include definitions of terms used; special education team visions concerning…

  4. 76 FR 30890 - Special Local Regulations; Sabine River, Orange, TX

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-27

    ... SECURITY Coast Guard 33 CFR Part 100 RIN 1625-AA08 Special Local Regulations; Sabine River, Orange, TX... River, Orange, Texas on September 24-25, 2011. This Special Local Regulation is intended to restrict... race in conjunction with the Orange, TX S.P.O.R.T. boat races. The powerboat race and associated...

  5. Update on vaccine-derived polioviruses - worldwide, July 2012-December 2013.

    PubMed

    Diop, Ousmane M; Burns, Cara C; Wassilak, Steven G; Kew, Olen M

    2014-03-21

    In 1988, the World Health Assembly resolved to eradicate poliomyelitis worldwide. One of the main tools used in polio eradication efforts has been live, attenuated oral poliovirus vaccine (OPV), an inexpensive vaccine easily administered by trained volunteers. OPV might require several doses to induce immunity, but then it provides long-term protection against paralytic disease through durable humoral immunity. Rare cases of vaccine-associated paralytic poliomyelitis can occur among immunologically normal OPV recipients, their contacts, and persons who are immunodeficient. In addition, vaccine-derived polioviruses (VDPVs) can emerge in areas with low OPV coverage to cause polio outbreaks and can replicate for years in persons who have primary, B-cell immunodeficiencies. This report updates previous surveillance summaries and describes VDPVs detected worldwide during July 2012-December 2013. Those include a new circulating VDPV (cVDPV) outbreak identified in Pakistan in 2012, with spread to Afghanistan; an outbreak in Afghanistan previously identified in 2009 that continued into 2013; a new outbreak in Chad that spread to Cameroon, Niger, and northeastern Nigeria; and an outbreak that began in Somalia in 2008 that continued and spread to Kenya in 2013. A large outbreak in Nigeria that was identified in 2005 was nearly stopped by the end of 2013. Additionally, 10 newly identified persons in eight countries were found to excrete immunodeficiency-associated VDPVs (iVDPVs), and VDPVs were found among immunocompetent persons and environmental samples in 13 countries. Because the majority of VDPV isolates are type 2, the World Health Organization has developed a plan for coordinated worldwide replacement of trivalent OPV (tOPV) with bivalent OPV (bOPV; types 1 and 3) by 2016, preceded by introduction of at least 1 dose of inactivated poliovirus vaccine (IPV) containing all three poliovirus serotypes into routine immunization schedules worldwide to ensure high population

  6. Expression of the poliovirus receptor in intestinal epithelial cells is not sufficient to permit poliovirus replication in the mouse gut.

    PubMed

    Zhang, S; Racaniello, V R

    1997-07-01

    Although the initial site of poliovirus replication in humans is the intestine, previously isolated transgenic mice which carry the human poliovirus receptor (PVR) gene (TgPVR mice), which develop poliomyelitis after intracerebral inoculation, are not susceptible to infection by the oral route. The low levels of PVR expressed in the TgPVR mouse intestine might explain the absence of poliovirus replication at that site. To ascertain whether PVR is the sole determinant of poliovirus susceptibility of the mouse intestine, we have generated transgenic mice by using the promoter for rat intestine fatty acid binding protein to direct PVR expression in mouse gut. Pvr was detected by immunohistochemistry in the enterocytes and M cells of transgenic mouse (TgFABP-PVR) small intestine. Upon oral inoculation with poliovirus, no increase in virus titer was detected in the feces of TgFABP-PVR mice, and no virus replication was observed in the small intestine, although poliovirus replicated in the brain after intracerebral inoculation. The failure of poliovirus to replicate in the TgFABP-PVR mouse small intestine was not due to lack of virus binding sites, because poliovirus could attach to fragments of small intestine from these mice. These results indicate that the inability of poliovirus to replicate in the mouse alimentary tract is not solely due to the absence of virus receptor, and other factors are involved in determining the ability of poliovirus to replicate in the mouse gut.

  7. [Circulating vaccine-derived poliovirus type 2 outbreak in Democratic Republic of Congo 2011-2012].

    PubMed

    Bazira, L; Coulibaly, T; Mayenga, M; Ncharre, C; Yogolelo, R; Mbule, A; Moudzeo, H; Lwamba, P; Mulumba, A W; Cabore, J

    2015-10-01

    According to the WHO records of 2013, the incidence of poliomyelitis was reduced by more than 99%, the number of endemic countries decreased from 125 in 1988 to 3 in 2013 and over 10 million cases were prevented from poliomyelitis thanks to the intensive use of Oral polio vaccine (OPV). However, the emergence of circulating vaccine-derived poliovirus strains (cVDPV), causing serious epidemics like the wild poliovirus, is a major challenge on the final straight towards the goal of eradication and OPV cessation. This paper describes the cVDPVoutbreak that occurred in the Democratic Republic of Congo (DRC) from November 2011 to April 2012. All children under 15 years of age with acute flaccid paralysis (AFP) and confirmed presence of cVDPV in the stool samples were included. Thirty (30) children, all from the administrative territories of Bukama and Malemba Nkulu in the Katanga Province (south-east DRC), were reported. The virus responsible was the cVDPV type 2 (0.7% -3.5% divergent from the reference Sabin 2 strain) in 29 children (97%) and the ambiguous vaccine-derived poliovirus strain (0.7% divergent) was confirmed in one case (3%), a boy seventeen months old and already vaccinated four times with OPV. Twentyfive children (83%) were protected by any of the routine EPI vaccines and 3 children (10%) had never received any dose of OPV. In reaction, DRC has conducted five local campaigns over a period of 10 months (from January to October 2012) and the epidemic was stopped after the second round performed in March 2012. As elsewhere in similar conditions, low immunization coverage, poor sanitation conditions and the stop of the use of OPV2 have favoured the emergence of the third cVDPV epidemic in DRC. The implementation of the Strategic Plan for Polio eradication and endgame strategic plan 2013-2018 will prevent the emergence of cVDPV and set up the conditions for a coordinated OPV phase out.

  8. Parallel path: poliovirus research in the vaccine era.

    PubMed

    Garfinkel, Michele S; Sarewitz, Daniel

    2003-07-01

    One goal of the scientific research enterprise is to improve the lives of individuals and the overall health of societies. This goal is achieved through a combination of factors, including the composition of research portfolios. In turn, this composition is determined by a variety of scientific and societal needs. The recent history of polio research highlights the complex relations between research policy, scientific progress and societal benefits. Here, we briefly review the circumstances leading to the possibility of eradication of poliovirus, evaluate the research environment that emerged following the introduction of a vaccine, and compare and contrast the current research framework with that for other infectious diseases. From this analysis, policy lessons with general applicability to scientific research are identified.

  9. Isolation and characterisation of poliovirus mutants resistant to heating at 50 degrees Celsius for 30 min.

    PubMed

    Shiomi, Hiroshi; Urasawa, Tomoko; Urasawa, Shozo; Kobayashi, Nobumichi; Abe, Shibobu; Taniguchi, Koki

    2004-11-01

    Poliovirus is heat-labile; on heating at 50 degrees Celsius for 30 min its infectivity decreases drastically and its antigenicity reverts from N to H. However, mutants resistant to heating at 50 degrees Celsius for 30 min from the Sabin 1 and 2 viruses were isolated by repeating the process of incubation of the virus stock at 50 degrees Celsius for 30 min and multiplication of the remaining virus in a cell culture. The isolated mutants were stable genetically, and maintained the rct and d markers of the parent virus. On electron microscopical examination, the mutants were observed to retain the intact morphology after being heated at 50 degrees Celsius for 30 min, while the parent virus was converted to empty particles devoid of RNA under the same conditions. On determination of the nucleotide sequence of the P1 region, a single nucleotide sequence substitution was detected at nucleotide no. 2741, resulting in an amino acid change from valine to alanine at the 87th position of VP1. This amino acid might be associated with the heat-resistance of the mutants. Furthermore, it was found that the thermostable mutants obtained in this study, which are resistant to "high" temperature (50 degrees Celsius) for a short time (30 min), were not stable against heating at the ambient temperature (37 degrees Celsius) for a long time (5 or 7 days). This suggests that the inactivation at high temperature for a short time and that at ambient temperature for a long time involve different mechanisms.

  10. Genetically Thermo-Stabilised, Immunogenic Poliovirus Empty Capsids; a Strategy for Non-replicating Vaccines

    PubMed Central

    Fox, Helen; Minor, Philip D.

    2017-01-01

    While wild type polio has been nearly eradicated there will be a need to continue immunisation programmes for some time because of the possibility of re-emergence and the existence of long term excreters of poliovirus. All vaccines in current use depend on growth of virus and most of the non-replicating (inactivated) vaccines involve wild type viruses known to cause poliomyelitis. The attenuated vaccine strains involved in the eradication programme have been used to develop new inactivated vaccines as production is thought safer. However it is known that the Sabin vaccine strains are genetically unstable and can revert to a virulent transmissible form. A possible solution to the need for virus growth would be to generate empty viral capsids by recombinant technology, but hitherto such particles are so unstable as to be unusable. We report here the genetic manipulation of the virus to generate stable empty capsids for all three serotypes. The particles are shown to be extremely stable and to generate high levels of protective antibodies in animal models. PMID:28103317

  11. Rapid diagnosis of poliovirus infection by PCR amplification.

    PubMed Central

    Chezzi, C

    1996-01-01

    A single-tube, single-primer-set reverse transcription-PCR assay was developed for the rapid detection of polioviruses in infected tissue culture fluids and clinical materials. The poliovirus-specific PCR primers are located in the VP1-2A region of the poliovirus genome. They generate a 290-bp product and can be used in duplex reactions with general enterovirus primers. The primers span the region used for genotype determination, so that genotype analysis of wild-type polioviruses can be performed by direct sequencing of the PCR products. Of 125 virus isolates typed as polioviruses by neutralization assays, 125 (100%) were also positive by PCR, and of 38 isolates typed as non-polio enteroviruses by conventional techniques, 38 (100%) were also negative by PCR. The assay described here is rapid, highly sensitive, and specific and has clinical applicability in the diagnosis of poliovirus infections. PMID:8784577

  12. Cell-Free, De Nova Synthesis of Poliovirus

    NASA Astrophysics Data System (ADS)

    Molla, Akhteruzzaman; Paul, Aniko V.; Wimmer, Eckard

    1991-12-01

    Cell-free translation of poliovirus RNA in an extract of uninfected human (HeLa) cells yielded viral proteins through proteolysis of the polyprotein. In the extract, newly synthesized proteins catalyzed poliovirus-specific RNA synthesis, and formed infectious poliovirus de novo. Newly formed virions were neutralized by type-specific antiserum, and infection of human cells with them was prevented by poliovirus receptor-specific antibodies. Poliovirus synthesis was increased nearly 70-fold when nucleoside triphosphates were added, but it was abolished in the presence of inhibitors of translation or viral genome replication. The ability to conduct cell-free synthesis of poliovirus will aid in the study of picornavirus proliferation and in the search for the control of picornaviral disease.

  13. Twenty-Eight Years of Poliovirus Replication in an Immunodeficient Individual: Impact on the Global Polio Eradication Initiative

    PubMed Central

    Dunn, Glynis; Klapsa, Dimitra; Wilton, Thomas; Stone, Lindsay; Minor, Philip D.; Martin, Javier

    2015-01-01

    There are currently huge efforts by the World Health Organization and partners to complete global polio eradication. With the significant decline in poliomyelitis cases due to wild poliovirus in recent years, rare cases related to the use of live-attenuated oral polio vaccine assume greater importance. Poliovirus strains in the oral vaccine are known to quickly revert to neurovirulent phenotype following replication in humans after immunisation. These strains can transmit from person to person leading to poliomyelitis outbreaks and can replicate for long periods of time in immunodeficient individuals leading to paralysis or chronic infection, with currently no effective treatment to stop excretion from these patients. Here, we describe an individual who has been excreting type 2 vaccine-derived poliovirus for twenty eight years as estimated by the molecular clock established with VP1 capsid gene nucleotide sequences of serial isolates. This represents by far the longest period of excretion described from such a patient who is the only identified individual known to be excreting highly evolved vaccine-derived poliovirus at present. Using a range of in vivo and in vitro assays we show that the viruses are very virulent, antigenically drifted and excreted at high titre suggesting that such chronic excreters pose an obvious risk to the eradication programme. Our results in virus neutralization assays with human sera and immunisation-challenge experiments using transgenic mice expressing the human poliovirus receptor indicate that while maintaining high immunisation coverage will likely confer protection against paralytic disease caused by these viruses, significant changes in immunisation strategies might be required to effectively stop their occurrence and potential widespread transmission. Eventually, new stable live-attenuated polio vaccines with no risk of reversion might be required to respond to any poliovirus isolation in the post-eradication era. PMID:26313548

  14. Twenty-Eight Years of Poliovirus Replication in an Immunodeficient Individual: Impact on the Global Polio Eradication Initiative.

    PubMed

    Dunn, Glynis; Klapsa, Dimitra; Wilton, Thomas; Stone, Lindsay; Minor, Philip D; Martin, Javier

    2015-08-01

    There are currently huge efforts by the World Health Organization and partners to complete global polio eradication. With the significant decline in poliomyelitis cases due to wild poliovirus in recent years, rare cases related to the use of live-attenuated oral polio vaccine assume greater importance. Poliovirus strains in the oral vaccine are known to quickly revert to neurovirulent phenotype following replication in humans after immunisation. These strains can transmit from person to person leading to poliomyelitis outbreaks and can replicate for long periods of time in immunodeficient individuals leading to paralysis or chronic infection, with currently no effective treatment to stop excretion from these patients. Here, we describe an individual who has been excreting type 2 vaccine-derived poliovirus for twenty eight years as estimated by the molecular clock established with VP1 capsid gene nucleotide sequences of serial isolates. This represents by far the longest period of excretion described from such a patient who is the only identified individual known to be excreting highly evolved vaccine-derived poliovirus at present. Using a range of in vivo and in vitro assays we show that the viruses are very virulent, antigenically drifted and excreted at high titre suggesting that such chronic excreters pose an obvious risk to the eradication programme. Our results in virus neutralization assays with human sera and immunisation-challenge experiments using transgenic mice expressing the human poliovirus receptor indicate that while maintaining high immunisation coverage will likely confer protection against paralytic disease caused by these viruses, significant changes in immunisation strategies might be required to effectively stop their occurrence and potential widespread transmission. Eventually, new stable live-attenuated polio vaccines with no risk of reversion might be required to respond to any poliovirus isolation in the post-eradication era.

  15. Encapsidation of poliovirus replicons encoding the complete human immunodeficiency virus type 1 gag gene by using a complementation system which provides the P1 capsid protein in trans.

    PubMed Central

    Porter, D C; Ansardi, D C; Morrow, C D

    1995-01-01

    replicon RNA from virus stocks after 21 serial passages of the replicon genomes with VV-P1 indicated that the replicon which contained the VP4 coding region was present at a higher level than the replicon which contained a complete substitution of the P1 capsid sequences. These differences in encapsidation, though, were not detected after only two serial passages of the replicons with VV-P1 or upon coinfection and serial passage with type 1 Sabin poliovirus.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:7853488

  16. Nonhomologous recombination between defective poliovirus and coxsackievirus genomes suggests a new model of genetic plasticity for picornaviruses.

    PubMed

    Holmblat, Barbara; Jégouic, Sophie; Muslin, Claire; Blondel, Bruno; Joffret, Marie-Line; Delpeyroux, Francis

    2014-08-05

    Most of the circulating vaccine-derived polioviruses (cVDPVs) implicated in poliomyelitis outbreaks in Madagascar have been shown to be recombinants between the type 2 poliovirus (PV) strain of the oral polio vaccine (Sabin 2) and another species C human enterovirus (HEV-C), such as type 17 coxsackie A virus (CA17) in particular. We studied intertypic genetic exchanges between PV and non-PV HEV-C by developing a recombination model, making it possible to rescue defective type 2 PV RNA genomes with a short deletion at the 3' end by the cotransfection of cells with defective or infectious CA17 RNAs. We isolated over 200 different PV/CA17 recombinants, using murine cells expressing the human PV receptor (PVR) and selecting viruses with PV capsids. We found some homologous (H) recombinants and, mostly, nonhomologous (NH) recombinants presenting duplications of parental sequences preferentially located in the regions encoding proteins 2A, 2B, and 3A. Short duplications appeared to be stable, whereas longer duplications were excised during passaging in cultured cells or after multiplication in PVR-transgenic mice, generating H recombinants with diverse sites of recombination. This suggests that NH recombination events may be a transient, intermediate step in the generation and selection of the fittest H recombinants. In addition to the classical copy-choice mechanism of recombination thought to generate mostly H recombinants, there may also be a modular mechanism of recombination, involving NH recombinant precursors, shaping the genomes of recombinant enteroviruses and other picornaviruses. Importance: The multiplication of circulating vaccine-derived polioviruses (cVDPVs) in poorly immunized human populations can render these viruses pathogenic, causing poliomyelitis outbreaks. Most cVDPVs are intertypic recombinants between a poliovirus (PV) strain and another human enterovirus, such as type 17 coxsackie A viruses (CA17). For further studies of the genetic exchanges

  17. Interrupting the transmission of wild polioviruses with vaccines: immunological considerations.

    PubMed Central

    Ghendon, Y.; Robertson, S. E.

    1994-01-01

    In 1988 the World Health Assembly set the goal of global poliomyelitis eradication by the year 2000. Substantial progress has been made, and 143 countries reported no poliomyelitis cases associated with the wild virus in 1993. This article reviews the immunological considerations relevant to interrupting the transmission of wild polioviruses with vaccines. Although serum immunity prevents poliomyelitis in the individual, it is local immunity that is important in preventing the transmission of polioviruses in the community. Natural infection and vaccination with oral polioviruses vaccine (OPV) produce local immunity in the intestine and the nasopharynx in about 70-80% of individuals. In contrast, inactivated poliovirus vaccine (IPV) produces local intestinal immunity in only 20-30% of the individuals. With either vaccine, however, a substantial proportion of the immunized population can transmit the wild virus. Moreover, although serum immunity is long-lasting, limited data suggest that local immunity may not be as persistent. To interrupt the transmission of wild polioviruses efforts should be made to achieve and sustain high levels of poliovirus vaccine coverage. Recent outbreaks show that wild poliovirus poses a risk for unimmunized individuals, even when overall coverage levels are high. Delivery of poliovirus vaccine to hard-to-reach populations will be of increasing importance as countries progress toward the final stages of poliomyelitis eradication. The immunization status of persons from poliomyelitis-free countries should be updated prior to travel to poliomyelitis-endemic areas. PMID:7867144

  18. 21 CFR 866.3405 - Poliovirus serological reagents.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Poliovirus serological reagents. 866.3405 Section 866.3405 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES..., some of these reagents consist of poliovirus antisera conjugated with a fluorescent...

  19. 21 CFR 866.3405 - Poliovirus serological reagents.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Poliovirus serological reagents. 866.3405 Section 866.3405 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES..., some of these reagents consist of poliovirus antisera conjugated with a fluorescent...

  20. 21 CFR 866.3405 - Poliovirus serological reagents.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Poliovirus serological reagents. 866.3405 Section 866.3405 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES..., some of these reagents consist of poliovirus antisera conjugated with a fluorescent...

  1. 21 CFR 866.3405 - Poliovirus serological reagents.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Poliovirus serological reagents. 866.3405 Section 866.3405 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES..., some of these reagents consist of poliovirus antisera conjugated with a fluorescent...

  2. 21 CFR 866.3405 - Poliovirus serological reagents.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Poliovirus serological reagents. 866.3405 Section 866.3405 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES..., some of these reagents consist of poliovirus antisera conjugated with a fluorescent...

  3. Environmental Isolation of Circulating Vaccine-Derived Poliovirus After Interruption of Wild Poliovirus Transmission - Nigeria, 2016.

    PubMed

    Etsano, Andrew; Damisa, Eunice; Shuaib, Faisal; Nganda, Gatei Wa; Enemaku, Ogu; Usman, Samuel; Adeniji, Adekunle; Jorba, Jaume; Iber, Jane; Ohuabunwo, Chima; Nnadi, Chimeremma; Wiesen, Eric

    2016-08-05

    In September 2015, more than 1 year after reporting its last wild poliovirus (WPV) case in July 2014 (1), Nigeria was removed from the list of countries with endemic poliovirus transmission,* leaving Afghanistan and Pakistan as the only remaining countries with endemic WPV. However, on April 29, 2016, a laboratory-confirmed, circulating vaccine-derived poliovirus type 2 (cVDPV2) isolate was reported from an environmental sample collected in March from a sewage effluent site in Maiduguri Municipal Council, Borno State, a security-compromised area in northeastern Nigeria. VDPVs are genetic variants of the vaccine viruses with the potential to cause paralysis and can circulate in areas with low population immunity. The Nigeria National Polio Emergency Operations Center initiated emergency response activities, including administration of at least 2 doses of oral poliovirus vaccine (OPV) to all children aged <5 years through mass campaigns; retroactive searches for missed cases of acute flaccid paralysis (AFP), and enhanced environmental surveillance. Approximately 1 million children were vaccinated in the first OPV round. Thirteen previously unreported AFP cases were identified. Enhanced environmental surveillance has not resulted in detection of additional VDPV isolates. The detection of persistent circulation of VDPV2 in Borno State highlights the low population immunity, surveillance limitations, and risk for international spread of cVDPVs associated with insurgency-related insecurity. Increasing vaccination coverage with additional targeted supplemental immunization activities and reestablishment of effective routine immunization activities in newly secured and difficult-to-reach areas in Borno is urgently needed.

  4. Vaccine-derived mutation in motif D of poliovirus RNA-dependent RNA polymerase lowers nucleotide incorporation fidelity.

    PubMed

    Liu, Xinran; Yang, Xiaorong; Lee, Cheri A; Moustafa, Ibrahim M; Smidansky, Eric D; Lum, David; Arnold, Jamie J; Cameron, Craig E; Boehr, David D

    2013-11-08

    All viral RNA-dependent RNA polymerases (RdRps) have a conserved structural element termed motif D. Studies of the RdRp from poliovirus (PV) have shown that a conformational change of motif D leads to efficient and faithful nucleotide addition by bringing Lys-359 into the active site where it serves as a general acid. The RdRp of the Sabin I vaccine strain has Thr-362 changed to Ile. Such a drastic change so close to Lys-359 might alter RdRp function and contribute in some way to the attenuated phenotype of Sabin type I. Here we present our characterization of the T362I RdRp. We find that the T362I RdRp exhibits a mutator phenotype in biochemical experiments in vitro. Using NMR, we show that this change in nucleotide incorporation fidelity correlates with a change in the structural dynamics of motif D. A recombinant PV expressing the T362I RdRp exhibits normal growth properties in cell culture but expresses a mutator phenotype in cells. For example, the T362I-containing PV is more sensitive to the mutagenic activity of ribavirin than wild-type PV. Interestingly, the T362I change was sufficient to cause a statistically significant reduction in viral virulence. Collectively, these studies suggest that residues of motif D can be targeted when changes in nucleotide incorporation fidelity are desired. Given the observation that fidelity mutants can serve as vaccine candidates, it may be possible to use engineering of motif D for this purpose.

  5. Interruption of poliovirus transmission in Ghana: molecular epidemiology of wild-type 1 poliovirus isolated from 1995 to 2008.

    PubMed

    Odoom, John Kofi; Forrest, Lindsay; Dunn, Glynis; Osei-Kwasi, Mubarak; Obodai, Evangeline; Arthur-Quarm, Jacob; Barnor, Jacob; Minor, Philip D; Martin, Javier

    2012-10-01

    Described in detail is the molecular epidemiology of wild-type 1 poliovirus circulation in Ghana between 1995-2008, following the implementation of a surveillance system for cases of acute flaccid paralysis and poliovirus infection. Molecular phylogenetic analysis combined with a detailed evaluation of epidemiological indicators revealed that the geographical and temporal circulation of wild-type poliovirus in Ghana was determined by the quality of the implementation of global eradication strategies. The transmission of "indigenous" wild-type 1 poliovirus was eliminated in 1999. However, a drastic reduction in national immunization campaigns resulted in the importation in 2003 and 2008 of wild-type 1 poliovirus from neighboring countries. Both outbreaks were promptly interrupted following resumption of immunization activities. The results detailed here provide scientific evidence that supports the feasibility of polio eradication in Central West Africa, one of the remaining endemic areas for the disease, provided that comprehensive immunization campaigns and sensitive surveillance systems are in place.

  6. Some characteristics of poliovirus strains isolated in Uganda between 1966 and 1971.

    PubMed

    Balayan, M S; Dömök, I; Fayinka, O A; Soneji, A D

    1976-01-01

    Sixty-five poliovirus strains were investigated in genetic marker tests in order to obtain information on the characteristics of polioviruses circulating in Uganda where, owing to the insufficient use of live poliovirus vaccine, poliomyelitis remained a serious public health problem. Of the type 1 strains predominant in both epidemic and non-epidemic years, 29 were studied for their antigenic fine structure. Based on their intratypic character, these strains proved to represent six different antigenic variants. Three of these variants were predominant during certain periods; the first variant was present in 1966 and 1968, the second in 1967, and the third from 1969 to the end of observation period. Four strains from Kuwait and three from Ghana isolated in 1969 and 1970 showed an antigenic structure identical to that of the strains predominant in Uganda in these years. Some strains proved to be of vaccine origin. Twenty-nine type 1 and 24 type 2 strains showed a great variety of characteristics when studied in d, od, and rct/40 marker tests. There was no indication that the distribution of strains according to their in vitro markers would have been different in epidemic and non-epidemic years, or that any particular combination of markers would have been more common among strains isolated from paralytic patients than among those from non-paralytic patients. Nine of 12 type 3 strains had the rct/40(+) marker.

  7. Some characteristics of poliovirus strains isolated in Uganda between 1966 and 1971*

    PubMed Central

    Balayan, M. S.; Dömök, I.; Fayinka, O. A.; Soneji, A. D.

    1976-01-01

    Sixty-five poliovirus strains were investigated in genetic marker tests in order to obtain information on the characteristics of polioviruses circulating in Uganda where, owing to the insufficient use of live poliovirus vaccine, poliomyelitis remained a serious public health problem. Of the type 1 strains predominant in both epidemic and non-epidemic years, 29 were studied for their antigenic fine structure. Based on their intratypic character, these strains proved to represent six different antigenic variants. Three of these variants were predominant during certain periods; the first variant was present in 1966 and 1968, the second in 1967, and the third from 1969 to the end of observation period. Four strains from Kuwait and three from Ghana isolated in 1969 and 1970 showed an antigenic structure identical to that of the strains predominant in Uganda in these years. Some strains proved to be of vaccine origin. Twenty-nine type 1 and 24 type 2 strains showed a great variety of characteristics when studied in d, od, and rct/40 marker tests. There was no indication that the distribution of strains according to their in vitro markers would have been different in epidemic and non-epidemic years, or that any particular combination of markers would have been more common among strains isolated from paralytic patients than among those from non-paralytic patients. Nine of 12 type 3 strains had the rct/40+ marker. PMID:186208

  8. 33 CFR 165.806 - Sabine Neches Waterway, Texas-regulated navigation area.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Sabine Neches Waterway, Texas... § 165.806 Sabine Neches Waterway, Texas—regulated navigation area. (a) The following is a regulated... thereto. (b) Unless otherwise authorized by the Captain of the Port, Port Arthur, Texas, tows on a hawser...

  9. 33 CFR 80.840 - Sabine Pass, TX to Galveston, TX.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 1 2012-07-01 2012-07-01 false Sabine Pass, TX to Galveston, TX. 80.840 Section 80.840 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY INTERNATIONAL NAVIGATION RULES COLREGS DEMARCATION LINES Eighth District § 80.840 Sabine Pass, TX to Galveston...

  10. 33 CFR 80.840 - Sabine Pass, TX to Galveston, TX.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 1 2013-07-01 2013-07-01 false Sabine Pass, TX to Galveston, TX. 80.840 Section 80.840 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY INTERNATIONAL NAVIGATION RULES COLREGS DEMARCATION LINES Eighth District § 80.840 Sabine Pass, TX to Galveston...

  11. 33 CFR 80.840 - Sabine Pass, TX to Galveston, TX.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Sabine Pass, TX to Galveston, TX. 80.840 Section 80.840 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY INTERNATIONAL NAVIGATION RULES COLREGS DEMARCATION LINES Eighth District § 80.840 Sabine Pass, TX to Galveston...

  12. 33 CFR 80.840 - Sabine Pass, TX to Galveston, TX.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 1 2014-07-01 2014-07-01 false Sabine Pass, TX to Galveston, TX. 80.840 Section 80.840 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY INTERNATIONAL NAVIGATION RULES COLREGS DEMARCATION LINES Eighth District § 80.840 Sabine Pass, TX to Galveston...

  13. 78 FR 44937 - Sabine Pass Liquefaction, LLC; Application for Long-Term Authorization To Export Liquefied...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-25

    ... authorization to export LNG from the Sabine Pass LNG Terminal in Cameron Parish, Louisiana, both to: (i) Any... and vaporization terminal in Cameron, Parish, Louisiana (Liquefaction Project). On April 16, 2012, the... proposed fifth train at the Sabine Pass Liquefaction Project in Cameron Parish, Louisiana, to: (i) Any...

  14. Nonhomologous Recombination between Defective Poliovirus and Coxsackievirus Genomes Suggests a New Model of Genetic Plasticity for Picornaviruses

    PubMed Central

    Holmblat, Barbara; Jégouic, Sophie; Muslin, Claire; Blondel, Bruno; Joffret, Marie-Line

    2014-01-01

    ABSTRACT Most of the circulating vaccine-derived polioviruses (cVDPVs) implicated in poliomyelitis outbreaks in Madagascar have been shown to be recombinants between the type 2 poliovirus (PV) strain of the oral polio vaccine (Sabin 2) and another species C human enterovirus (HEV-C), such as type 17 coxsackie A virus (CA17) in particular. We studied intertypic genetic exchanges between PV and non-PV HEV-C by developing a recombination model, making it possible to rescue defective type 2 PV RNA genomes with a short deletion at the 3′ end by the cotransfection of cells with defective or infectious CA17 RNAs. We isolated over 200 different PV/CA17 recombinants, using murine cells expressing the human PV receptor (PVR) and selecting viruses with PV capsids. We found some homologous (H) recombinants and, mostly, nonhomologous (NH) recombinants presenting duplications of parental sequences preferentially located in the regions encoding proteins 2A, 2B, and 3A. Short duplications appeared to be stable, whereas longer duplications were excised during passaging in cultured cells or after multiplication in PVR-transgenic mice, generating H recombinants with diverse sites of recombination. This suggests that NH recombination events may be a transient, intermediate step in the generation and selection of the fittest H recombinants. In addition to the classical copy-choice mechanism of recombination thought to generate mostly H recombinants, there may also be a modular mechanism of recombination, involving NH recombinant precursors, shaping the genomes of recombinant enteroviruses and other picornaviruses. PMID:25096874

  15. Albert Sabin and the Coalition to Eliminate Polio from the Americas.

    PubMed

    Hampton, Lee

    2009-01-01

    Albert B. Sabin, MD, developer of the oral polio vaccine, was also a major proponent of its use in annual vaccination campaigns aimed at the elimination of polio. Sabin argued that administering his vaccine simultaneously to every child in a country would break polio's chains of transmission. Although he was already promoting mass vaccination by the 1960s, Sabin's efforts expanded considerably when he became an adviser to groups fighting polio in the Americas in the 1980s. Sabin's experiences provide a window into both the formation of the coalition that eliminated poliomyelitis from the Western Hemisphere and what can happen when biomedical researchers become public health policy advisers. Although the polio elimination coalition succeeded in part because member groups often accommodated each other's priorities, Sabin was often limited by his indifference to the interests of those he was advising and to the shortcomings of his vaccine.

  16. Albert Sabin and the Coalition to Eliminate Polio From the Americas

    PubMed Central

    2009-01-01

    Albert B. Sabin, MD, developer of the oral polio vaccine, was also a major proponent of its use in annual vaccination campaigns aimed at the elimination of polio. Sabin argued that administering his vaccine simultaneously to every child in a country would break polio's chains of transmission. Although he was already promoting mass vaccination by the 1960s, Sabin's efforts expanded considerably when he became an adviser to groups fighting polio in the Americas in the 1980s. Sabin's experiences provide a window into both the formation of the coalition that eliminated poliomyelitis from the Western Hemisphere and what can happen when biomedical researchers become public health policy advisers. Although the polio elimination coalition succeeded in part because member groups often accommodated each other's priorities, Sabin was often limited by his indifference to the interests of those he was advising and to the shortcomings of his vaccine. PMID:19008524

  17. Battle against poliovirus in Pakistan.

    PubMed

    Fatima, Kaneez; Qadri, Ishtiaq

    2013-11-15

    On 22 Feb 2013, the Polio Monitoring Cell of Pakistan announced that the 2012-2013 polio campaign ended, and that 1.6 million children could not be vaccinated due to security concerns in several regions where polio workers had been killed. Those who could not be vaccinated included 50,000 children from the Federally Administrated Tribal Area (FATA), 150,000 form Khyber Pakhtoon Khao, 400,000 from a Quetta, 400,000 from Karachi, and a small number from the Rawalpindi District. These statistics are worrying, as several districts in the large metropolitan cities of Karachi and Quetta were also excluded. The fear of advanced medicine, ideas, or complex devices is a new phenomenon in many conservative and poor countries such as Pakistan, Afghanistan, Sudan, and Somalia. To safeguard the safety of the rest of the world, the failure in the implementation of WHO guidelines for vaccination must be regulated by the UN. There are a number of reasons for the phobias surrounding vaccination, but as technology continues to evolve at such a rapid rate, those with self-determined ideologies cannot cope with such advances. They become vocal to gain popularity and prevent the use of these technologies and medicine by creating and spreading rumors and propaganda of expediency. The struggle to vaccinate children is not easily understood by anyone living in the developed world. The irrational fear of vaccines and the lack of vaccination pose a serious global health risk and must be curbed through a wide variety of pro-vaccination media and religious campaigns.

  18. Poliovirus aggregates and their survival in water.

    PubMed Central

    Young, D C; Sharp, D G

    1977-01-01

    Inactivation of aggregated poliovirus by bromine is characterized by a continuously decreasing reaction rate. Poliovirus released from infected cells in these experiments by alternate freezing and thawing in water without electrolytes has always been aggregated. The aggregates persist even on 7,000-fold dilution in ion-free water. Virus similarly released into phosphate-buffered saline solution may be well dispersed, but it aggregates when sedimented into a salt-free sucrose gradient or when it is diluted as little as 10-fold in water. Large one-step dilutions of dispersed virus in water remain dispersed. Aggregated virus was not dispersed by one-step dilution (7,000-fold) in distilled or untreated lake water but was dispersed if phosphate-buffered saline or clarified secondary sewage plant effluent was used as diluent. Dispersed virus aggregates at all dilutions in alum-treated, finished water from the city filter plant. This may be the result of complex formation with insoluble material rather than virion-virion aggregation. A simple procedure is described for rendering a very dilute suspension of mixed virion aggregates into a three-part spectrum of sizes. Images PMID:189686

  19. Circulating vaccine-derived polioviruses: current state of knowledge.

    PubMed Central

    Kew, Olen M.; Wright, Peter F.; Agol, Vadim I.; Delpeyroux, Francis; Shimizu, Hiroyuki; Nathanson, Neal; Pallansch, Mark A.

    2004-01-01

    Within the past 4 years, poliomyelitis outbreaks associated with circulating vaccine-derived polioviruses (cVDPVs) have occurred in Hispaniola (2000-01), the Philippines (2001), and Madagascar (2001-02). Retrospective studies have also detected the circulation of endemic cVDPV in Egypt (1988-93) and the likely localized spread of oral poliovirus vaccine (OPV)-derived virus in Belarus (1965-66). Gaps in OPV coverage and the previous eradication of the corresponding serotype of indigenous wild poliovirus were the critical risk factors for all cVDPV outbreaks. The cVDPV outbreaks were stopped by mass immunization campaigns using OPV. To increase sensitivity for detecting vaccine-derived polioviruses (VDPVs), in 2001 the Global Polio Laboratory Network implemented additional testing requirements for all poliovirus isolates under investigation. This approach quickly led to the recognition of the Philippines and Madagascar cVDPV outbreaks, but of no other current outbreaks. The potential risk of cVDPV emergence has increased dramatically in recent years as wild poliovirus circulation has ceased in most of the world. The risk appears highest for the type 2 OPV strain because of its greater tendency to spread to contacts. The emergence of cVDPVs underscores the critical importance of eliminating the last pockets of wild poliovirus circulation, maintaining universally high levels of polio vaccine coverage, stopping OPV use as soon as it is safely possible to do so, and continuing sensitive poliovirus surveillance into the foreseeable future. Particular attention must be given to areas where the risks for wild poliovirus circulation have been highest, and where the highest rates of polio vaccine coverage must be maintained to suppress cVDPV emergence. PMID:15106296

  20. Increasing Type 1 Poliovirus Capsid Stability by Thermal Selection

    PubMed Central

    Adeyemi, Oluwapelumi O.; Nicol, Clare

    2016-01-01

    ABSTRACT Poliomyelitis is a highly infectious disease caused by poliovirus (PV). It can result in paralysis and may be fatal. Integrated global immunization programs using live-attenuated oral (OPV) and/or inactivated (IPV) PV vaccines have systematically reduced its spread and paved the way for eradication. Immunization will continue posteradication to ensure against reintroduction of the disease, but there are biosafety concerns for both OPV and IPV. They could be addressed by the production and use of virus-free virus-like particle (VLP) vaccines that mimic the “empty” capsids (ECs) normally produced in viral infection. Although ECs are antigenically indistinguishable from mature virus particles, they are less stable and readily convert into an alternative conformation unsuitable for vaccine purposes. Stabilized ECs, expressed recombinantly as VLPs, could be ideal candidate vaccines for a polio-free world. However, although genome-free PV ECs have been expressed as VLPs in a variety of systems, their inherent antigenic instability has proved a barrier to further development. In this study, we selected thermally stable ECs of type 1 PV (PV-1). The ECs are antigenically stable at temperatures above the conversion temperature of wild-type (wt) virions. We have identified mutations on the capsid surface and in internal networks that are responsible for EC stability. With reference to the capsid structure, we speculate on the roles of these residues in capsid stability and postulate that such stabilized VLPs could be used as novel vaccines. IMPORTANCE Poliomyelitis is a highly infectious disease caused by PV and is on the verge of eradication. There are biosafety concerns about reintroduction of the disease from current vaccines that require live virus for production. Recombinantly expressed virus-like particles (VLPs) could address these inherent problems. However, the genome-free capsids (ECs) of wt PV are unstable and readily change antigenicity to a form not

  1. Poliovirus sampling by using sodium dodecyl sulfate/EDTA-pretreated chromatography paper strips.

    PubMed

    Maes, Piet; Van Doren, Els; Denys, Barbara; Thoelen, Inge; Rahman, Mustafizur; Vijgen, Leen; Van Ranst, Marc

    2004-12-17

    To achieve the goal of poliovirus eradication, surveillance of endemic areas is a crucial step in the poliovirus eradication program. Currently, six countries still have endemic poliovirus. We have tested a novel method which uses SDS/EDTA-treated chromatography paper strips to collect and transport poliovirus-containing stool samples. The SDS/EDTA-treated paper strips were soaked with different dilutions of poliovirus-containing feces and stored at different temperatures. After storing the SDS/EDTA paper strips for 5 months at 37 degrees C, poliovirus RNA could be successfully amplified using RT-PCR. Infectivity of wild-type poliovirus type 1, 2, and 3 was lost upon contact with the SDS/EDTA-treated strips. This easy, inexpensive, and biosafe chromatography paper strip method for the collection and transportation of poliovirus samples can be of use in poliovirus surveillance and polio vaccination programs.

  2. Poliovirus protein 2BC increases cytosolic free calcium concentrations.

    PubMed Central

    Aldabe, R; Irurzun, A; Carrasco, L

    1997-01-01

    Poliovirus-infected cells undergo an increase in cytoplasmic calcium concentrations from the 4th h postinfection. The protein responsible for this effect was identified by the expression of different poliovirus nonstructural proteins in HeLa cells by using a recombinant vaccinia virus system. Synthesis of protein 2BC enhances cytoplasmic calcium concentrations in a manner similar to that observed in poliovirus-infected cells. To identify the regions in 2BC involved in modifying cytoplasmic calcium levels, several 2BC variants were generated. Regions present in both 2B and 2C are necessary to augment cellular free calcium levels. Therefore, in addition to inducing proliferation of membranous vesicles, poliovirus protein 2BC also alters cellular calcium homeostasis. PMID:9223520

  3. Poliovirus protease 3C(pro) kills cells by apoptosis.

    PubMed

    Barco, A; Feduchi, E; Carrasco, L

    2000-01-20

    The tetracycline-based Tet-Off expression system has been used to analyze the effects of poliovirus protease 3C(pro) on human cells. Stable HeLa cell clones that express this poliovirus protease under the control of an inducible, tightly regulated promoter were obtained. Tetracycline removal induces synthesis of 3C protease, followed by drastic morphological alterations and cellular death. Degradation of cellular DNA in nucleosomes and generation of apoptotic bodies are observed from the second day after 3C(pro) induction. The cleavage of poly(ADP-ribose) polymerase, an enzyme involved in DNA repair, occurs after induction of 3C(pro), indicating caspase activation by this poliovirus protease. The 3C(pro)-induced apoptosis is blocked by the caspase inhibitor z-VAD-fmk. Our findings suggest that the protease 3C is responsible for triggering apoptosis in poliovirus-infected cells by a mechanism that involves caspase activation. Copyright 2000 Academic Press.

  4. Preventing Vaccine-Derived Poliovirus Emergence during the Polio Endgame

    PubMed Central

    Burns, Cara C.; Lyons, Hil; Blake, Isobel M.; Oberste, M. Steven; Kew, Olen M.; Grassly, Nicholas C.

    2016-01-01

    Reversion and spread of vaccine-derived poliovirus (VDPV) to cause outbreaks of poliomyelitis is a rare outcome resulting from immunisation with the live-attenuated oral poliovirus vaccines (OPVs). Global withdrawal of all three OPV serotypes is therefore a key objective of the polio endgame strategic plan, starting with serotype 2 (OPV2) in April 2016. Supplementary immunisation activities (SIAs) with trivalent OPV (tOPV) in advance of this date could mitigate the risks of OPV2 withdrawal by increasing serotype-2 immunity, but may also create new serotype-2 VDPV (VDPV2). Here, we examine the risk factors for VDPV2 emergence and implications for the strategy of tOPV SIAs prior to OPV2 withdrawal. We first developed mathematical models of VDPV2 emergence and spread. We found that in settings with low routine immunisation coverage, the implementation of a single SIA increases the risk of VDPV2 emergence. If routine coverage is 20%, at least 3 SIAs are needed to bring that risk close to zero, and if SIA coverage is low or there are persistently “missed” groups, the risk remains high despite the implementation of multiple SIAs. We then analysed data from Nigeria on the 29 VDPV2 emergences that occurred during 2004−2014. Districts reporting the first case of poliomyelitis associated with a VDPV2 emergence were compared to districts with no VDPV2 emergence in the same 6-month period using conditional logistic regression. In agreement with the model results, the odds of VDPV2 emergence decreased with higher routine immunisation coverage (odds ratio 0.67 for a 10% absolute increase in coverage [95% confidence interval 0.55−0.82]). We also found that the probability of a VDPV2 emergence resulting in poliomyelitis in >1 child was significantly higher in districts with low serotype-2 population immunity. Our results support a strategy of focused tOPV SIAs before OPV2 withdrawal in areas at risk of VDPV2 emergence and in sufficient number to raise population immunity

  5. Preventing Vaccine-Derived Poliovirus Emergence during the Polio Endgame.

    PubMed

    Pons-Salort, Margarita; Burns, Cara C; Lyons, Hil; Blake, Isobel M; Jafari, Hamid; Oberste, M Steven; Kew, Olen M; Grassly, Nicholas C

    2016-07-01

    Reversion and spread of vaccine-derived poliovirus (VDPV) to cause outbreaks of poliomyelitis is a rare outcome resulting from immunisation with the live-attenuated oral poliovirus vaccines (OPVs). Global withdrawal of all three OPV serotypes is therefore a key objective of the polio endgame strategic plan, starting with serotype 2 (OPV2) in April 2016. Supplementary immunisation activities (SIAs) with trivalent OPV (tOPV) in advance of this date could mitigate the risks of OPV2 withdrawal by increasing serotype-2 immunity, but may also create new serotype-2 VDPV (VDPV2). Here, we examine the risk factors for VDPV2 emergence and implications for the strategy of tOPV SIAs prior to OPV2 withdrawal. We first developed mathematical models of VDPV2 emergence and spread. We found that in settings with low routine immunisation coverage, the implementation of a single SIA increases the risk of VDPV2 emergence. If routine coverage is 20%, at least 3 SIAs are needed to bring that risk close to zero, and if SIA coverage is low or there are persistently "missed" groups, the risk remains high despite the implementation of multiple SIAs. We then analysed data from Nigeria on the 29 VDPV2 emergences that occurred during 2004-2014. Districts reporting the first case of poliomyelitis associated with a VDPV2 emergence were compared to districts with no VDPV2 emergence in the same 6-month period using conditional logistic regression. In agreement with the model results, the odds of VDPV2 emergence decreased with higher routine immunisation coverage (odds ratio 0.67 for a 10% absolute increase in coverage [95% confidence interval 0.55-0.82]). We also found that the probability of a VDPV2 emergence resulting in poliomyelitis in >1 child was significantly higher in districts with low serotype-2 population immunity. Our results support a strategy of focused tOPV SIAs before OPV2 withdrawal in areas at risk of VDPV2 emergence and in sufficient number to raise population immunity above the

  6. Exploring the fitness landscape of poliovirus

    NASA Astrophysics Data System (ADS)

    Bianco, Simone; Acevedo, Ashely; Andino, Raul; Tang, Chao

    2012-02-01

    RNA viruses are known to display extraordinary adaptation capabilities to different environments, due to high mutation rates. Their very dynamical evolution is captured by the quasispecies concept, according to which the viral population forms a swarm of genetic variants linked through mutation, which cooperatively interact at a functional level and collectively contribute to the characteristics of the population. The description of the viral fitness landscape becomes paramount towards a more thorough understanding of the virus evolution and spread. The high mutation rate, together with the cooperative nature of the quasispecies, makes it particularly challenging to explore its fitness landscape. I will present an investigation of the dynamical properties of poliovirus fitness landscape, through both the adoption of new experimental techniques and theoretical models.

  7. Poliovirus: Generation, Quantification, Propagation, Purification, and Storage

    PubMed Central

    Burrill, Cecily P.; Strings, Vanessa R.; Andino, Raul

    2016-01-01

    Poliovirus (PV) is the prototypical picornavirus. It is a non-enveloped RNA virus with a small (~7.5 kb) genome of positive polarity. It has long served as a model to study RNA virus biology, pathogenesis, and evolution. cDNA clones of several strains are available, and infectious virus can be produced by the transfection of in vitro transcribed viral genomes into an appropriate host cell. PV infects many human and non-human primate cell lines including HeLa and HeLa S3 cells, and can grow to high titer in culture. Protocols for the production, propagation, quantification, and purification of PV are presented. A separate chapter concerning the generation and characterization of PV mutants will also be presented. PMID:23686830

  8. Environmental surveillance for polioviruses in the Global Polio Eradication Initiative.

    PubMed

    Asghar, Humayun; Diop, Ousmane M; Weldegebriel, Goitom; Malik, Farzana; Shetty, Sushmitha; El Bassioni, Laila; Akande, Adefunke O; Al Maamoun, Eman; Zaidi, Sohail; Adeniji, Adekunle J; Burns, Cara C; Deshpande, Jagadish; Oberste, M Steve; Lowther, Sara A

    2014-11-01

    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.

  9. Construction and characterization of poliovirus subgenomic replicons

    SciTech Connect

    Kaplan, G.; Racaniello, V.R. )

    1988-05-01

    Poliovirus RNAs containing in-frame deletions within the capsid-coding region were produced by in vitro transcription of altered poliovirus type 1 cDNA by using bacteriophage T7 RNA polymerase. Three RNAs were transcribed that contained deletions of 2,317 nucleotides (bases 747 to 3,064), 1,781 nucleotides (bases 1,175 to 2,956), and 1,295 nucleotides (bases 1,175 to 2,470). All three subgenomic RNAs replicated after transfection into HeLa cells, demonstrating that sequences encoding the capsid polypeptides are not essential for viral RNA replication in vivo. Viral RNA containing the largest deletion (R1) replicated approximately three times better than full-length RNA produced in vitro. Northern blot (RNA blot) hybridization analysis of total cellular RNA from HeLa cells at different times after transfection with R1 demonstrated the presence of increasing amounts of the expected 5.1-kilobase subgenomic RNA. Analysis by immunoprecipitation of ({sup 35}S-labeled) viral proteins induced after transfection of R1 RNA into HeLa cells revealed the presence of proteins 2A{sup pro}, 2C, and 3D{sup pol} and its precursors, suggesting that the polyprotein cleavages are similar to those occurring in virus-infected cells. These internally and terminally deleted RNAs inhibited the replication of subgenomic replicons R1, R2, and R3 and caused a reduction in plaque size when cotransfected with P1/Mahoney or P2/Lansing viral RNA, suggesting that individual cells had received both RNAs.

  10. [Analysis of dissemination pathways for poliovirus].

    PubMed

    Ohka, Seii

    2009-06-01

    Poliomyelitis is an acute disease of the central nervous system (CNS) caused by poliovirus (PV). In humans, an infection is initiated by oral ingestion of the virus, followed by multiplication in the alimentary mucosa, from which the virus spreads through the bloodstream. Paralytic poliomyelitis initiates from the invasion of the central nervous system by circulating poliovirus, probably via the blood-brain barrier. After the virus enters the central nervous system, it replicates in neurons, especially in motor neurons, inducing the cell death that causes paralytic poliomyelitis. Along with this route of dissemination, a neuron-specific pathway has been reported in humans, monkeys, and PV-sensitive transgenic (Tg) mice carrying the PV receptor (hPVR/CD155) gene. It is important for the efficient virus dissemination to overcome the barriers as follows; i) to access the target tissue, ii) to enter the cells, iii) to reach the place for the replication, iv) to replicate efficiently. PV is easily transferred to humans orally; however, no rodent model for oral infections has been developed. We analyzed the each barrier above, and showed that PV is inactivated by the low pH of the gastric contents in mice. We also demonstrated that type 1 interferon signaling plays an important role in determining permissivity in the alimentary tract. As for the neural pathway, we demonstrated that direct efficient interaction between the cytoplasmic domain and cytoplasmic dynein is essential for the efficient retrograde transport of PV-containing vesicles along microtubules for the hPVR-dependent PV transport. On the other hand, we found that hPVR-independent axonal transport of PV was also observed in hPVR-Tg and non-Tg mice, indicating that several different pathways for PV axonal transport exist.

  11. 78 FR 13241 - Drawbridge Operation Regulation; Sabine River, Near Ruliff, LA

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-27

    ... Ruliff, LA AGENCY: Coast Guard, DHS. ACTION: Final rule. SUMMARY: The Coast Guard is removing the... Sabine River, mile 36.2, between Newton County, TX and Calcasieu Parish, LA. The drawbridge was...

  12. Development and consideration of global policies for managing the future risks of poliovirus outbreaks: insights and lessons learned through modeling.

    PubMed

    Thompson, Kimberly M; Duintjer Tebbens, Radboud J; Pallansch, Mark A; Kew, Olen M; Sutter, Roland W; Aylward, R Bruce; Watkins, Margaret; Gary, Howard; Alexander, James P; Venczel, Linda; Johnson, Denise; Cáceres, Victor M; Sangrujee, Nalinee; Jafari, Hamid; Cochi, Stephen L

    2006-12-01

    The success of the Global Polio Eradication Initiative promises to bring large benefits, including sustained improvements in quality of life (i.e., cases of paralytic disease and deaths avoided) and costs saved from cessation of vaccination. Obtaining and maintaining these benefits requires that policymakers manage the transition from the current massive use of oral poliovirus vaccine (OPV) to a world without OPV and free of the risks of potential future reintroductions of live polioviruses. This article describes the analytical journey that began in 2001 with a retrospective case study on polio risk management and led to development of dynamic integrated risk, economic, and decision analysis tools to inform global policies for managing the risks of polio. This analytical journey has provided several key insights and lessons learned that will be useful to future analysts involved in similar complex decision-making processes.

  13. Sit Down with Sabin: Venkat Srinivasan: The Future of Batteries (LBNL Summer Lecture Series)

    SciTech Connect

    Russell, Sabin; Srinivasan, Venkat

    2011-06-29

    Lawrence Berkeley National Laboratory battery scientist Venkat Srinivasan appears June 29, 2011 on "Sit Down with Sabin," a weekly conversation in which former reporter Sabin Russell chats with Berkeley Lab staff about innovative science. Over the course of several conversations held at noon in the Building 50 auditorium, Russell and Lab staff will explore the ups and downs of pioneering science — all without the aid of PowerPoints. Brought to you by Berkeley Lab Public Affairs.

  14. Sit Down With Sabin: Merrian Fuller: Efficiency for sale. Who's buying? (LBNL Summer Lecture Series)

    SciTech Connect

    Fuller, Merrian; Russell, Sabin

    2011-07-26

    Merrian Fuller from the Environmental Energy Technologies Division appeared on July 26th, 2011 for this installment of "Sit Down with Sabin," a conversation in which former reporter Sabin Russell chats with Lab staff about innovative science. They will discuss "Efficiency for Sale. Who's Buying?" During this series of conversations, Russell and Lab staff will explore the ups and downs of pioneering science, all without the aid of PowerPoints.

  15. Sit Down with Sabin: Henrik Scheller: Customizing plants for biofuels. (LBNL Summer Lecture Series)

    ScienceCinema

    Sabin, Russell; Scheller, Henrik

    2016-07-12

    Henrik Scheller from the JBEI appeared on August 3rd, 2011 for this installment of "Sit Down with Sabin," a conversation in which former reporter Sabin Russell chats with Lab staff about innovative science. They will discuss "Customizing plants for biofuels." During this series of conversations, Russell and Lab staff will explore the ups and downs of pioneering science, all without the aid of PowerPoints.

  16. Seroepidemiology of Polioviruses among University Students in Northern Italy

    PubMed Central

    Baldo, Vincenzo; Cocchio, Silvia; Lazzari, Roberta; Saracino, Elena; Bertoncello, Chiara; Buja, Alessandra; Trevisan, Andrea

    2012-01-01

    The widespread use of poliovirus vaccination schemes has led to a marked decline in the incidence of paralytic poliomyelitis worldwide, but wild poliovirus is still endemic in some developing countries, and in 2009 a total of 23 countries reported at least 1 case of poliomyelitis caused by wild-strain polio viruses. A serological survey was thus conducted on the immunological status against polioviruses of 318 young adults, classified by their country of origin. Immunity to poliomyelitis was assessed by neutralizing antibody titration in tissues cultured on microplates. The rate of seronegativity (≤1:8) in the study population was 26.7% for poliovirus type 1, 7.2% for type 2, and 22.6% for type 3. In our sample of 318 individuals, 219 (68.9%) were Italian and 99 (31.1%) were from outside the European Union (EU). The proportion of cases found seropositive to polioviruses 1 and 3 decreased significantly with older age; this age-related decrease was more evident in the Italian group than among the non-EU subjects. Any risk of the wild virus recurring and causing paralytic poliomyelitis must be prevented, keeping Europe polio free by means of appropriate immunological protection, until polio has been conclusively eradicated all over the world. Judging from our findings, it may be worth considering administering a fifth dose of polio vaccine to adolescents. PMID:22739695

  17. Infectivity of RNA from Inactivated Poliovirus

    PubMed Central

    Nuanualsuwan, Suphachai; Cliver, Dean O.

    2003-01-01

    During inactivation of poliovirus type 1 (PV-1) by exposure to UV, hypochlorite, and heat (72°C), the infectivity of the virus was compared with that of its RNA. DEAE-dextran (1-mg/ml concentration in Dulbecco's modified Eagle medium buffered with 0.05 M Tris, pH 7.4) was used to facilitate transfecting PV-1 RNA into FRhK-4 host cells. After interaction of PV-1 RNA with cell monolayer at room temperature (21 to 22°C) for 20 min, the monolayers were washed with 5 ml of Hanks balanced salt solution. The remainder of the procedure was the same as that for the conventional plaque technique, which was also used for quantifying the PV-1 whole-particle infectivity. Plaque formation by extracted RNA was approximately 100,000-fold less efficient than that by whole virions. The slopes of best-fit regression lines of inactivation curves for virion infectivity and RNA infectivity were compared to determine the target of inactivation. For UV and hypochlorite inactivation the slopes of inactivation curves of virion infectivity and RNA infectivity were not statistically different. However, the difference of slopes of inactivation curves of virion infectivity and RNA infectivity was statistically significant for thermal inactivation. The results of these experiments indicate that viral RNA is a primary target of UV and hypochlorite inactivations but that the sole target of thermal inactivation is the viral capsid. PMID:12620852

  18. Comprehensive screening for immunodeficiency-associated vaccine-derived poliovirus: an essential oral poliovirus vaccine cessation risk management strategy.

    PubMed

    Duintjer Tebbens, R J; Thompson, K M

    2017-01-01

    If the world can successfully control all outbreaks of circulating vaccine-derived poliovirus that may occur soon after global oral poliovirus vaccine (OPV) cessation, then immunodeficiency-associated vaccine-derived polioviruses (iVDPVs) from rare and mostly asymptomatic long-term excretors (defined as ⩾6 months of excretion) will become the main source of potential poliovirus outbreaks for as long as iVDPV excretion continues. Using existing models of global iVDPV prevalence and global long-term poliovirus risk management, we explore the implications of uncertainties related to iVDPV risks, including the ability to identify asymptomatic iVDPV excretors to treat with polio antiviral drugs (PAVDs) and the transmissibility of iVDPVs. The expected benefits of expanded screening to identify and treat long-term iVDPV excretors with PAVDs range from US$0.7 to 1.5 billion with the identification of 25-90% of asymptomatic long-term iVDPV excretors, respectively. However, these estimates depend strongly on assumptions about the transmissibility of iVDPVs and model inputs affecting the global iVDPV prevalence. For example, the expected benefits may decrease to as low as US$260 million with the identification of 90% of asymptomatic iVDPV excretors if iVDPVs behave and transmit like partially reverted viruses instead of fully reverted viruses. Comprehensive screening for iVDPVs will reduce uncertainties and maximize the expected benefits of PAVD use.

  19. Methods for recovering poliovirus and rotavirus from oysters.

    PubMed Central

    Speirs, J I; Pontefract, R D; Harwig, J

    1987-01-01

    Polioviruses and rotaviruses are potential indicators of sewage pollution of water and shellfish. Several methods for detecting these viruses in oysters were assessed. Elution-precipitation involving Catfloc for clarification and skim milk for subsequent flocculation resulted in the recovery of an average of 79% of poliovirus type 1 and 37% of rotavirus SA-11 from oyster homogenates inoculated with low numbers of these viruses. Adsorption-elution-precipitation did not improve the recovery of poliovirus and was detrimental to the recovery of rotavirus. Ultrafiltration or ultracentrifugation resulted in improved recovery of rotavirus but also in higher toxicity of oyster extracts to cell cultures. We recommend the use of the described elution-precipitation method for detecting viral pollutants in sample of oysters. PMID:2827573

  20. Robustness against serum neutralization of a poliovirus type 1 from a lethal epidemic of poliomyelitis in the Republic of Congo in 2010.

    PubMed

    Drexler, Jan Felix; Grard, Gilda; Lukashev, Alexander N; Kozlovskaya, Liubov I; Böttcher, Sindy; Uslu, Gökhan; Reimerink, Johan; Gmyl, Anatoly P; Taty-Taty, Raphaël; Lekana-Douki, Sonia Etenna; Nkoghe, Dieudonné; Eis-Hübinger, Anna M; Diedrich, Sabine; Koopmans, Marion; Leroy, Eric M; Drosten, Christian

    2014-09-02

    In 2010, a large outbreak of poliomyelitis with unusual 47% lethality occurred in Pointe Noire, Republic of Congo. Vaccine-mediated immunity against the outbreak virus was never investigated. A wild poliovirus 1 (WPV1) isolated from a fatal case (termed PV1-RC2010) showed a previously unknown combination of amino acid exchanges in critical antigenic site 2 (AgS2, VP1 capsid protein positions 221SAAL → 221PADL). These exchanges were also detected in an additional 11 WPV1 strains from fatal cases. PV1-RC2010 escaped neutralization by three different mAbs relevant for AgS2. Virus neutralization was tested in sera from fatal cases, who died before supplementary immunization (n = 24), Gabonese recipients of recent oral polio vaccination (n = 12), routinely vaccinated German medical students (n = 34), and German outpatients tested for antipoliovirus immunity (n = 17) on Vero, human rhabdomyosarcoma, and human epidermoid carcinoma 2 cells. Fatal poliomyelitis cases gave laboratory evidence of previous trivalent vaccination. Neutralizing antibody titers against PV1-RC2010 were significantly lower than those against the vaccine strain Sabin-1, two genetically distinct WPV1s isolated in 1965 and 2010 and two genetically distinct vaccine-derived PV strains. Of German vaccinees tested according to World Health Organization protocols, 15-29% were unprotected according to their neutralization titers (<1:8 serum dilution), even though all were protected against Sabin-1. Phylogenetic analysis of the WPV1 outbreak strains suggested a recent introduction of virus progenitors from Asia with formation of separate Angolan and Congolese lineages. Only the latter carried both critical AgS2 mutations. Antigenetically variant PVs may become relevant during the final phase of poliomyelitis eradication in populations with predominantly vaccine-derived immunity. Sustained vaccination coverage and clinical and environmental surveillance will be necessary.

  1. Robustness against serum neutralization of a poliovirus type 1 from a lethal epidemic of poliomyelitis in the Republic of Congo in 2010

    PubMed Central

    Drexler, Jan Felix; Grard, Gilda; Lukashev, Alexander N.; Kozlovskaya, Liubov I.; Böttcher, Sindy; Uslu, Gökhan; Reimerink, Johan; Gmyl, Anatoly P.; Taty-Taty, Raphaël; Lekana-Douki, Sonia Etenna; Nkoghe, Dieudonné; Eis-Hübinger, Anna M.; Diedrich, Sabine; Koopmans, Marion; Leroy, Eric M.; Drosten, Christian

    2014-01-01

    In 2010, a large outbreak of poliomyelitis with unusual 47% lethality occurred in Pointe Noire, Republic of Congo. Vaccine-mediated immunity against the outbreak virus was never investigated. A wild poliovirus 1 (WPV1) isolated from a fatal case (termed PV1-RC2010) showed a previously unknown combination of amino acid exchanges in critical antigenic site 2 (AgS2, VP1 capsid protein positions 221SAAL→221PADL). These exchanges were also detected in an additional 11 WPV1 strains from fatal cases. PV1-RC2010 escaped neutralization by three different mAbs relevant for AgS2. Virus neutralization was tested in sera from fatal cases, who died before supplementary immunization (n = 24), Gabonese recipients of recent oral polio vaccination (n = 12), routinely vaccinated German medical students (n = 34), and German outpatients tested for antipoliovirus immunity (n = 17) on Vero, human rhabdomyosarcoma, and human epidermoid carcinoma 2 cells. Fatal poliomyelitis cases gave laboratory evidence of previous trivalent vaccination. Neutralizing antibody titers against PV1-RC2010 were significantly lower than those against the vaccine strain Sabin-1, two genetically distinct WPV1s isolated in 1965 and 2010 and two genetically distinct vaccine-derived PV strains. Of German vaccinees tested according to World Health Organization protocols, 15–29% were unprotected according to their neutralization titers (<1:8 serum dilution), even though all were protected against Sabin-1. Phylogenetic analysis of the WPV1 outbreak strains suggested a recent introduction of virus progenitors from Asia with formation of separate Angolan and Congolese lineages. Only the latter carried both critical AgS2 mutations. Antigenetically variant PVs may become relevant during the final phase of poliomyelitis eradication in populations with predominantly vaccine-derived immunity. Sustained vaccination coverage and clinical and environmental surveillance will be necessary. PMID:25136105

  2. Annual report of the Australian National Poliovirus Reference Laboratory, 2008.

    PubMed

    Roberts, Jason A; Grant, Kristina A; Yoon, Yeon Kyung; Polychronopoulos, Sophie; Ibrahim, Aishah; Thorley, Bruce R

    2009-09-01

    The Australian National Poliovirus Reference Laboratory (NPRL) is accredited by the World Health Organization (WHO) for the testing of stool specimens from cases of acute flaccid paralysis (AFP), a major clinical presentation of poliovirus infection. The NPRL, in collaboration with the Australian Paediatric Surveillance Unit, co-ordinates surveillance for cases of AFP in children in Australia, according to criteria recommended by the WHO. Clinical specimens are referred from AFP cases in children and suspected case of poliomyelitis in persons of any age. The WHO AFP surveillance performance indicator for a polio-free country such as Australia, is 1 non-polio AFP case per 100,000 children less than 15 years of age. In 2008, the Polio Expert Committee (PEC) classified 62 cases as non-polio AFP, or 1.51 non-polio AFP cases per 100,000 children aged less than 15 years. Poliovirus infection is confirmed by virus culture of stool specimens from AFP cases as other conditions that present with acute paralysis can mimic polio. While no poliovirus was reported in Australia from any source in 2008, the non-polio enteroviruses echovirus 25, coxsackievirus B2 and echovirus 11 were isolated from stool specimens of AFP cases. The last report of a wild poliovirus in Australia was due to an importation from Pakistan in 2007. With 4 countries remaining endemic for poliomyelitis--Afghanistan, India, Nigeria and Pakistan--and more than 1,600 confirmed cases of wild poliovirus infection in 18 countries in 2008, Australia continues to be at risk of further importation events.

  3. Update on Vaccine-Derived Polioviruses - Worldwide, January 2014-March 2015.

    PubMed

    Diop, Ousmane M; Burns, Cara C; Sutter, Roland W; Wassilak, Steven G; Kew, Olen M

    2015-06-19

    Since the World Health Assembly's 1988 resolution to eradicate poliomyelitis, one of the main tools of the World Health Organization (WHO) Global Polio Eradication Initiative (GPEI) has been the live, attenuated oral poliovirus vaccine (OPV). OPV might require several doses to induce immunity but provides long-term protection against paralytic disease. Through effective use of OPV, GPEI has brought polio to the threshold of eradication. Wild poliovirus type 2 (WPV2) was eliminated in 1999, WPV3 has not been detected since November 2012, and WPV1 circulation appears to be restricted to parts of Pakistan and Afghanistan. However, continued use of OPV carries two key risks. The first, vaccine-associated paralytic poliomyelitis (VAPP) has been recognized since the early 1960s. VAPP is a very rare event that occurs sporadically when an administered dose of OPV reverts to neurovirulence and causes paralysis in the vaccine recipient or a nonimmune contact. VAPP can occur among immunologically normal vaccine recipients and their contacts as well as among persons who have primary immunodeficiencies (PIDs) manifested by defects in antibody production; it is not associated with outbreaks. The second, the emergence of genetically divergent, neurovirulent vaccine-derived polioviruses (VDPVs) was recognized more recently. Circulating VDPVs (cVDPVs) resemble WPVs and, in areas with low OPV coverage, can cause polio outbreaks. Immunodeficiency-associated VDPVs (iVDPVs) can replicate and be excreted for years in some persons with PIDs; GPEI maintains a registry of iVDPV cases. Ambiguous VDPVs (aVDPVs) are isolates that cannot be classified definitively. This report updates previous surveillance summaries and describes VDPVs detected worldwide during January 2014-March 2015. Those include new cVDPV outbreaks in Madagascar and South Sudan, and sharply reduced type 2 cVDPV (cVDPV2) circulation in Nigeria and Pakistan during the latter half of 2014. Eight newly identified persons in

  4. [Precipitation antibodies against poliovirus in patients with poliomyelitis].

    PubMed

    Ruiz-Gómez, J; Bustamante, M E

    1977-01-01

    Sera from 26 children bearing poliomyelitis caused by virus tipe I and from 47 cases with paralysis of different etiology (non-poliomyelitic) were tested against antigen of poliovirus types I, II and III with an agar-immunoprecipitation reaction. All sera with neutralizing antibodies with titres of 1:1250 gave positive results in immunodifusion tests. The percentage of positiveness decrease with lower titres. No false positive reactions were found. Immunodiffusion test with antigens of poliovirus were positive in 100% of sera from patients with poliomyelitis and only in 30% in sera from patients with non polio paralysis.

  5. Individual-based modeling of potential poliovirus transmission in connected religious communities in North America with low uptake of vaccination.

    PubMed

    Kisjes, Kasper H; Duintjer Tebbens, Radboud J; Wallace, Gregory S; Pallansch, Mark A; Cochi, Stephen L; Wassilak, Steven G F; Thompson, Kimberly M

    2014-11-01

    Pockets of undervaccinated individuals continue to raise concerns about their potential to sustain epidemic transmission of vaccine-preventable diseases. Prior importations of live polioviruses (LPVs) into Amish communities in North America led to their recognition as a potential and identifiable linked network of undervaccinated individuals. We developed an individual-based model to explore the potential transmission of a LPV throughout the North American Amish population. Our model demonstrates the expected limited impact associated with the historical importations, which occurred in isolated communities during the low season for poliovirus transmission. We show that some conditions could potentially lead to wider circulation of LPVs and cases of paralytic polio in Amish communities if an importation occurred during or after 2013. The impact will depend on the uncertain historical immunity to poliovirus infection among members of the community. Heterogeneity in immunization coverage represents a risk factor for potential outbreaks of polio if introduction of a LPV occurs, although overall high population immunity in North America suggests that transmission would remain relatively limited. Efforts to prevent spread between Amish church districts with any feasible measures may offer the best opportunity to contain an outbreak and limit its size. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  6. Interaction of Poliovirus with Its Receptor Affords a High Level of Infectivity to the Virion in Poliovirus Infections Mediated by the Fc Receptor

    PubMed Central

    Arita, Minetaro; Horie, Hitoshi; Arita, Mineo; Nomoto, Akio

    1999-01-01

    Poliovirus infects susceptible cells through the poliovirus receptor (PVR), which functions to bind virus and to change its conformation. These two activities are thought to be necessary for efficient poliovirus infection. How binding and conformation conversion activities contribute to the establishment of poliovirus infection was investigated. Mouse L cells expressing mouse high-affinity Fcγ receptor molecules were established and used to study poliovirus infection mediated by mouse antipoliovirus monoclonal antibodies (MAbs) (immunoglobulin G2a [IgG2a] subtypes) or PVR-IgG2a, a chimeric molecule consisting of the extracellular moiety of PVR and the hinge and Fc portion of mouse IgG2a. The antibodies and PVR-IgG2a showed the same degree of affinity for poliovirus, but the infectivities mediated by these molecules were different. Among the molecules tested, PVR-IgG2a mediated the infection most efficiently, showing 50- to 100-fold-higher efficiency than that attained with the different MAbs. A conformational change of poliovirus was induced only by PVR-IgG2a. These results strongly suggested that some specific interaction(s) between poliovirus and the PVR is required for high-level infectivity of poliovirus in this system. PMID:9882307

  7. Hydrophobic Polycationic Coatings Disinfect Poliovirus and Rotavirus Solutions

    PubMed Central

    Larson, Alyssa M.; Hsu, Bryan B.; Rautaray, Debabrata; Haldar, Jayanta; Chen, Jianzhu

    2011-01-01

    Coating surfaces with N-alkylated polyethylenimines (PEIs), namely branched N,N-hexyl,methyl-PEI via covalent attachment to glass or linear N,N-dodecyl,methyl-PEI by physical deposition (“painting”) onto polyethylene, enables the resultant materials to quickly and efficiently disinfect aqueous solutions of (non-enveloped) poliovirus and rotavirus. PMID:20967804

  8. Stopping poliovirus vaccination after eradication: issues and challenges.

    PubMed Central

    Wood, D. J.; Sutter, R. W.; Dowdle, W. R.

    2000-01-01

    Since 1988 reported polio cases worldwide have declined by about 85% and the number of known or suspected polioendemic countries has decreased from over 120 to less than 50. With eradication of poliomyelitis approaching, issues potentially affecting when and how vaccination against poliovirus can be stopped become extremely important. Because of the potential risks and benefits inherent in such a decision, the best available science, a risk-benefit analysis, contingency plans, a stock pile of poliovirus vaccines, and the endorsement by the global policy-making committees will all be needed before vaccination can be discontinued. The scientific basis for stopping polio immunization has been reviewed by WHO. This Round Table article summarizes the current state of knowledge, provides an update on the processes and timelines for certification, containment, and stopping vaccination, and highlights some of the unanswered scientific questions that will be addressed by further research. These include whether transmission of vaccine-derived poliovirus strains could be sustained so that poliomyelitis could re-emerge in a future unvaccinated population and whether prolonged excretion of vaccine-derived poliovirus from individuals with immune deficiencies could be a mechanism through which this could occur. PMID:10812731

  9. Effects of Chlorine Concentration on the Structure of Poliovirus

    PubMed Central

    Alvarez, Maria E.; O'Brien, R. T.

    1982-01-01

    Chlorine concentrations below 0.8 mg/liter inactivated poliovirus without causing separation of the viral components. These results indicate that the release of RNA from the capsids is the result, not the cause, of virus inactivation by chlorine. PMID:6275791

  10. Hydrophobic polycationic coatings disinfect poliovirus and rotavirus solutions.

    PubMed

    Larson, Alyssa M; Hsu, Bryan B; Rautaray, Debabrata; Haldar, Jayanta; Chen, Jianzhu; Klibanov, Alexander M

    2011-03-01

    Coating surfaces with N-alkylated polyethylenimines (PEIs), namely branched N,N-hexyl,methyl-PEI via covalent attachment to glass or linear N,N-dodecyl,methyl-PEI by physical deposition ("painting") onto polyethylene, enables the resultant materials to quickly and efficiently disinfect aqueous solutions of (non-enveloped) poliovirus and rotavirus.

  11. INFECTIVITY OF RIBONUCLEIC ACID FROM POLIOVIRUS IN HUMAN CELL MONOLAYERS

    PubMed Central

    Alexander, Hattie E.; Koch, Gebhard; Mountain, Isabel Morgan; Van Damme, Olga

    1958-01-01

    Ribonucleic acid prepared by the method of Gierer and Schramm from concentrated and partially purified types I and II polioviruses has been demonstrated to be infectious for HeLa and human amnion cells in monolayers. In areas of cytopathogenic action resulting from invasion of cells by RNA, intact poliovirus, of the type from which the RNA had been prepared, is present. The infectivity of the RNA was completely inactivated by a 2 minute exposure to purified ribonuclease or to whole normal monkey serum shown to contain measurable concentrations of this enzyme. Whole virus infectivity was not influenced by RNAase or whole normal monkey serum. Normal and polio-immune globulin, desoxyribonuclease, lysozyme, proteolytic enzymes, and bovine albumin failed to inactivate the infectivity of RNA. The degree of infectivity of isolated RNA from poliovirus for cells in monolayer was greatly influenced by the ionic strength of the environment. The experimental evidence suggests that isolated poliovirus RNA is the carrier of the biological activity responsible for infection of cells and for transmission of genetic information which controls type specificity. PMID:13575680

  12. Polio eradication. Efficacy of inactivated poliovirus vaccine in India.

    PubMed

    Jafari, Hamid; Deshpande, Jagadish M; Sutter, Roland W; Bahl, Sunil; Verma, Harish; Ahmad, Mohammad; Kunwar, Abhishek; Vishwakarma, Rakesh; Agarwal, Ashutosh; Jain, Shilpi; Estivariz, Concepcion; Sethi, Raman; Molodecky, Natalie A; Grassly, Nicholas C; Pallansch, Mark A; Chatterjee, Arani; Aylward, R Bruce

    2014-08-22

    Inactivated poliovirus vaccine (IPV) is efficacious against paralytic disease, but its effect on mucosal immunity is debated. We assessed the efficacy of IPV in boosting mucosal immunity. Participants received IPV, bivalent 1 and 3 oral poliovirus vaccine (bOPV), or no vaccine. A bOPV challenge was administered 4 weeks later, and excretion was assessed 3, 7, and 14 days later. Nine hundred and fifty-four participants completed the study. Any fecal shedding of poliovirus type 1 was 8.8, 9.1, and 13.5% in the IPV group and 14.4, 24.1, and 52.4% in the control group by 6- to 11-month, 5-year, and 10-year groups, respectively (IPV versus control: Fisher's exact test P < 0.001). IPV reduced excretion for poliovirus types 1 and 3 between 38.9 and 74.2% and 52.8 and 75.7%, respectively. Thus, IPV in OPV-vaccinated individuals boosts intestinal mucosal immunity.

  13. Isolation and Characterization of Poliovirus in Cell Culture Systems.

    PubMed

    Thorley, Bruce R; Roberts, Jason A

    2016-01-01

    The isolation and characterization of enteroviruses by cell culture was accepted as the "gold standard" by clinical virology laboratories. Methods for the direct detection of all enteroviruses by reverse transcription polymerase chain reaction, targeting a conserved region of the genome, have largely supplanted cell culture as the principal diagnostic procedure. However, the World Health Organization's Global Polio Eradication Initiative continues to rely upon cell culture to isolate poliovirus due to the lack of a reliable sensitive genetic test for direct typing of enteroviruses from clinical specimens. Poliovirus is able to infect a wide range of mammalian cell lines, with CD155 identified as the primary human receptor for all three seroytpes, and virus replication leads to an observable cytopathic effect. Inoculation of cell lines with extracts of clinical specimens and subsequent passaging of the cells leads to an increased virus titre. Cultured isolates of poliovirus are suitable for testing by a variety of methods and remain viable for years when stored at low temperature.This chapter describes general procedures for establishing a cell bank and routine passaging of cell lines. While the sections on specimen preparation and virus isolation focus on poliovirus, the protocols are suitable for other enteroviruses.

  14. Polyadenylic acid at the 3'-terminus of poliovirus RNA.

    PubMed

    Yogo, Y; Wimmer, E

    1972-07-01

    Poliovirus RNA that has been derivatized at the 3'-end with NaIO(4)-NaB(3)H(4) yields, after hydrolysis with alkali or RNase T2, predominantly labeled residues of modified adenosine; no labeled nucleoside derivative is produced by digestion with RNase A or RNase T1. The 3'-terminal bases of the RNA are, therefore,...ApA(OH). Hydrolyzates of poliovirus [(32)P]RNA, after exhaustive digestion with RNase T1 or RNase A, contain, besides internal oligonucleotides, polynucleotides resistant to further action of ribonucleases T1 and A, respectively; these polynucleotides were isolated by membrane-filter binding or ion-exchange chromatography. The sequence of the T1-resistant polynucleotide was determined to be (Ap)(n)A(OH), that of the RNase A-resistant polynucleotide was GpGp(Ap)(n)A(OH). The chain length (n) of the polyadenylic acid, as analyzed by different methods, averages 89 nucleotides. Gel electrophoresis revealed heterogeneity of the size of poly(A). Poliovirus RNA, when labeled in vitro at the 3'-end, contains [3'-(3)H]poly(A); when labeled in vivo with [(3)H]A, it contains [(3)H](Ap)(n)A(OH). The data establish that... YpGpGp(Ap)([unk])A(OH) is the 3'-terminal sequence of poliovirus RNA, Type 1 (Mahoney). Since this mammalian virus reproduces in the cell cytoplasm, these observations may modify prior interpretations of the function of polyadenylate ends on messenger RNAs.

  15. Mechanisms of inactivation of poliovirus by chlorine dioxide and iodine.

    PubMed Central

    Alvarez, M E; O'Brien, R T

    1982-01-01

    Chlorine dioxide and iodine inactivated poliovirus more efficiently at pH 10.0 than at pH 6.0. Sedimentation analyses of viruses inactivated by chlorine dioxide and iodine at pH 10.9 showed that viral RNA separated from the capsids, resulting in the conversion of virions from 156S structures to 80S particles. The RNAs release from both chlorine dioxide- and iodine-inactivated viruses cosedimented with intact 35S viral RNA. Both chlorine dioxide and iodine reacted with the capsid proteins of poliovirus and changed the pI from pH 7.0 to pH 5.8. However, the mechanisms of inactivation of poliovirus by chlorine dioxide and iodine were found to differ. Iodine inactivated viruses by impairing their ability to adsorb to HeLa cells, whereas chlorine dioxide-inactivated viruses showed a reduced incorporation of [14C]uridine into new viral RNA. We concluded, then, that chlorine dioxide inactivated poliovirus by reacting with the viral RNA and impairing the ability of the viral genome to act as a template for RNA synthesis. PMID:6295277

  16. Sit Down with Sabin: Margaret Torn: The Carbon Cycle Like You've Never Seen It (LBNL Summer Lecture Series)

    SciTech Connect

    Russell, Sabin; Torn, Margaret

    2011-07-06

    Lawrence Berkeley National Laboratory soil scientist Margaret Torn appears July 6, 2011 on "Sit Down with Sabin," a weekly conversation in which former reporter Sabin Russell chats with Berkeley Lab staff about innovative science. Torn discusses how she travels the world to learn more about soil's huge role in the global carbon cycle. Brought to you by Berkeley Lab Public Affairs.

  17. 79 FR 69841 - Intent To Prepare a Draft Environmental Impact Statement for the Sabine Pass to Galveston Bay, TX...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2014-11-24

    ... present and those likely to be affected by potential future impacts of storm surge and ecosystem... and up to $30 million in property damage. Hurricane Rita in 2005 resulted in storm surge of 9.2 feet... produced storm surges of 14 feet near Sabine Pass and 11 to 12 feet across Sabine Lake. The City of Port...

  18. Parental attitudes toward multiple poliovirus injections following a provider recommendation.

    PubMed

    Kolasa, M S; Bisgard, K M; Prevots, D R; Desai, S N; Dibling, K

    2001-01-01

    Changes to the polio vaccination schedule, first to a sequential inactivated poliovirus/oral poliovirus (IPV/OPV) schedule in 1996 and most recently to an all-IPV schedule, require infants to receive additional injections. Some surveys show parental hesitation concerning extra injections, whereas others show that parents prefer multiple simultaneous injections over extra immunization visits. This study describes parental behavior and attitudes about the poliovirus vaccine recommendations and additional injections at the 2- and 4-month immunization visits. Beginning July 1, 1996, providers in eight public health clinics in Cobb and Douglas Counties, Georgia, informed parents of polio vaccination options and recommended the IPV/OPV sequential schedule. A cross-sectional clinic exit survey was conducted from July 15, 1996, to January 31, 1997, with parents whose infants (younger than 6 months) were eligible for a first poliovirus vaccination. Of approximately 405 eligible infants, parents of 293 infants were approached for an interview, and 227 agreed to participate. Of those 227 participants, 210 (92%) parents chose IPV for their infant and 17 (8%) chose OPV. Of greatest concern to most parents was vaccine-associated paralytic polio (VAPP) (155, or 68.3%); the next greatest concern was an extra injection (22, or 9.7%). These parental concerns were unrelated to the number of injections the infant actually received. After receiving information on polio vaccination options and a provider recommendation, parents overwhelmingly chose IPV over OPV. Concern about VAPP was more common than objection to an extra injection. The additional injection that results from using IPV for an infant's first poliovirus vaccination appears to be acceptable to most parents.

  19. High-Throughput Next-Generation Sequencing of Polioviruses.

    PubMed

    Montmayeur, Anna M; Ng, Terry Fei Fan; Schmidt, Alexander; Zhao, Kun; Magaña, Laura; Iber, Jane; Castro, Christina J; Chen, Qi; Henderson, Elizabeth; Ramos, Edward; Shaw, Jing; Tatusov, Roman L; Dybdahl-Sissoko, Naomi; Endegue-Zanga, Marie Claire; Adeniji, Johnson A; Oberste, M Steven; Burns, Cara C

    2017-02-01

    The poliovirus (PV) is currently targeted for worldwide eradication and containment. Sanger-based sequencing of the viral protein 1 (VP1) capsid region is currently the standard method for PV surveillance. However, the whole-genome sequence is sometimes needed for higher resolution global surveillance. In this study, we optimized whole-genome sequencing protocols for poliovirus isolates and FTA cards using next-generation sequencing (NGS), aiming for high sequence coverage, efficiency, and throughput. We found that DNase treatment of poliovirus RNA followed by random reverse transcription (RT), amplification, and the use of the Nextera XT DNA library preparation kit produced significantly better results than other preparations. The average viral reads per total reads, a measurement of efficiency, was as high as 84.2% ± 15.6%. PV genomes covering >99 to 100% of the reference length were obtained and validated with Sanger sequencing. A total of 52 PV genomes were generated, multiplexing as many as 64 samples in a single Illumina MiSeq run. This high-throughput, sequence-independent NGS approach facilitated the detection of a diverse range of PVs, especially for those in vaccine-derived polioviruses (VDPV), circulating VDPV, or immunodeficiency-related VDPV. In contrast to results from previous studies on other viruses, our results showed that filtration and nuclease treatment did not discernibly increase the sequencing efficiency of PV isolates. However, DNase treatment after nucleic acid extraction to remove host DNA significantly improved the sequencing results. This NGS method has been successfully implemented to generate PV genomes for molecular epidemiology of the most recent PV isolates. Additionally, the ability to obtain full PV genomes from FTA cards will aid in facilitating global poliovirus surveillance.

  20. Modelling Atmospheric Rivers and the Potential for Southeast Texas Flooding: A Case Study of the Maya Express and the March 2016 Sabine River Flood

    NASA Astrophysics Data System (ADS)

    McIntosh, J.; Lander, K.

    2016-12-01

    For three days in March of 2016, southeast Texas was inundated with up to 19 inches of rainfall, swelling the Sabine River to record flood stages. This event was attributed to an atmospheric river (AR), regionally known as the "Maya Express," which carried moisture from the Gulf of Mexico into the Sabine River Basin. Studies by the NOAA/NWS Climate Prediction Center have shown that ARs are occurring more frequently due to the intensification of El Niño that increases the available moisture in the atmosphere. In this study, we analyzed the hydrological and meteorological setup of the event on the Sabine River to characterize the flood threat associated with AR rainfall and simulated how an equivalent AR event would impact an urban basin in Houston, Texas. Our primary data sources included WSR-88D radar-based rainfall estimates and observed data at USGS river gauges. Furthermore, the land surface parameters evaluated included land cover, soil types, basin topology, model-derived soil moisture states, and topography. The spatial distribution of precipitation from the storm was then translated west over the Houston and used to force a hydrologic model to assess the impact of an event comparable to the March 2016 event on Houston's San Jacinto River Basin. The results indicate that AR precipitation poses a flood risk to urbanized areas in southeast Texas because of the low lying topography, impervious pavement, and limited flood control. Due to this hydrologic setup, intense AR rainfall can yield a rapid urban runoff response that overwhelms the river system, potentially endangering the lives and property of millions of people in the Houston area. Ultimately, if the frequency of AR development increases, regional flood potential may increase. Given the consequences established in this study, more research should be conducted in order to better predict the rate of recurrence and effects of Maya Express generated precipitation.

  1. Antibody titers against vaccine and contemporary wild poliovirus type 1 in children immunized with IPV+OPV and young adults immunized with OPV.

    PubMed

    Lukashev, Alexander N; Yarmolskaya, Maria S; Shumilina, Elena Yu; Sychev, Daniil A; Kozlovskaya, Liubov I

    2016-02-02

    In 2010, a type 1 poliovirus outbreak in Congo with 445 lethal cases was caused by a virus that was neutralized by sera of German adults vaccinated with inactivated polio vaccine with a reduced efficiency. This seroprevalence study was done in two cohorts immunized with other vaccination schedules. Russian children aged 3-6 years immunized with a combination of inactivated and live polio vaccines were reasonably well protected against any wild type poliovirus 1, including the Congolese isolate. Adults aged 20-29 years immunized only with live vaccine were apparently protected against the vaccine strain (92% seropositive), but only 50% had detectable antibodies against the Congo-2010 isolate. Both waning immunity and serological divergence of the Congolese virus could contribute to this result.

  2. Cretaceous and Tertiary compressional tectonics as cause of Sabine arch, eastern Texas and northwestern Louisiana

    SciTech Connect

    Jackson, M.L.W.; Laubach, S.E.

    1988-09-01

    The Sabine arch is a large (12,000 mi/sup 2/ or 31,080 km/sup 2/) low-amplitude anticline centered on the Texas-Louisiana border. A basement-cored feature formed in the Jurassic, the arch has been interpreted as (1) a Jurassic horst that persisted throughout the Cretaceous as a topographic relict of rifting, (2) a dome caused by deep-seated Cretaceous plutonism, and (3) a fold caused by regional tectonism. Using regional maps and cross sections derived from 811 well logs, they tested models of the Sabine arch origin by establishing arch movement history. Their results show that the horst and plutonic dome models do not adequately explain the cause of the Sabine arch.

  3. A host-specific, temperature-sensitive translation defect determines the attenuation phenotype of a human rhinovirus/poliovirus chimera, PV1(RIPO).

    PubMed

    Jahan, Nusrat; Wimmer, Eckard; Mueller, Steffen

    2011-07-01

    By using a rhinosvirus/poliovirus type 1 chimera, PV1(RIPO), with the cognate internal ribosome entry site (IRES) of human rhinovirus type 2 (HRV2), we set out to shed light on the mechanism by which this variant expresses its attenuated phenotype in poliovirus-sensitive, CD155 transgenic (tg) mice and cynomolgus monkeys. Here we report that replication of PV1(RIPO) is restricted not only in human cells of neuronal origin, as was reported previously, but also in cells of murine origin at physiological temperature. This block in replication was enhanced at 39.5°C but, remarkably, it was absent at 33°C. PV1(RIPO) variants that overcame the replication block were derived by serial passage under restrictive conditions in either mouse cells or human neuronal cells. All adapting mutations mapped to the 5'-nontranslated region of PV1(RIPO). Variants selected in mouse cells, but not in human neuronal cells, exhibited increased mouse neurovirulence in vivo. The observed strong mouse-specific defect of PV1(RIPO) at nonpermissive temperature correlated with the translational activity of the HRV2 IRES in this chimeric virus. These unexpected results must be kept in mind when poliovirus variants are tested in CD155 tg mice for their neurovirulent potential, particularly in assays of live attenuated oral poliovirus vaccine lots. Virulence may be masked by adverse species-specific conditions in mouse cells that may not allow accurate prediction of neurovirulence in the human host. Thus, novel poliovirus variants in line for possible development of human vaccines must be tested in nonhuman primates.

  4. Poly(rC) binding proteins mediate poliovirus mRNA stability.

    PubMed Central

    Murray, K E; Roberts, A W; Barton, D J

    2001-01-01

    The 5'-terminal 88 nt of poliovirus RNA fold into a cloverleaf RNA structure and form ribonucleoprotein complexes with poly(rC) binding proteins (PCBPs; AV Gamarnik, R Andino, RNA, 1997, 3:882-892; TB Parsley, JS Towner, LB Blyn, E Ehrenfeld, BL Semler, RNA, 1997, 3:1124-1134). To determine the functional role of these ribonucleoprotein complexes in poliovirus replication, HeLa S10 translation-replication reactions were used to quantitatively assay poliovirus mRNA stability, poliovirus mRNA translation, and poliovirus negative-strand RNA synthesis. Ribohomopoly(C) RNA competitor rendered wild-type poliovirus mRNA unstable in these reactions. A 5'-terminal 7-methylguanosine cap prevented the degradation of wild-type poliovirus mRNA in the presence of ribohomopoly(C) competitor. Ribohomopoly(A), -(G), and -(U) did not adversely affect poliovirus mRNA stability. Ribohomopoly(C) competitor RNA inhibited the translation of poliovirus mRNA but did not inhibit poliovirus negative-strand RNA synthesis when poliovirus replication proteins were provided in trans using a chimeric helper mRNA possessing the hepatitis C virus IRES. A C24A mutation prevented UV crosslinking of PCBPs to 5' cloverleaf RNA and rendered poliovirus mRNA unstable. A 5'-terminal 7-methylguanosine cap blocked the degradation of C24A mutant poliovirus mRNA. The C24A mutation did not inhibit the translation of poliovirus mRNA nor diminish viral negative-strand RNA synthesis relative to wild-type RNA. These data support the conclusion that poly(rC) binding protein(s) mediate the stability of poliovirus mRNA by binding to the 5'-terminal cloverleaf structure of poliovirus mRNA. Because of the general conservation of 5' cloverleaf RNA sequences among picornaviruses, including C24 in loop b of the cloverleaf, we suggest that viral mRNA stability of polioviruses, coxsackieviruses, echoviruses, and rhinoviruses is mediated by interactions between PCBPs and 5' cloverleaf RNA. PMID:11497431

  5. Sit Down with Sabin: David Schlegel: Hunting Dark Energy (LBNL Summer Lecture Series)

    SciTech Connect

    Russell, Sabin; Schlegel, David

    2011-06-22

    Lawrence Berkeley National Laboratory physicist and dark energy hunter David Schlegel chats with Sabin Russell, former San Francisco Chronicle reporter turned Berkeley Lab science writer, June 22, 2011. Their conversation is the first installment of "Sit Down With Sabin," a weekly conversation hosted by Russell. Over the course of five conversations with Berkeley Lab staff this summer, Russell will explore the ups and downs of innovative science — all without the aid of PowerPoint slides. Brought to you by Berkeley Lab Public Affairs.

  6. Spread of Vaccine-Derived Poliovirus from a Paralytic Case in an Immunodeficient Child: an Insight into the Natural Evolution of Oral Polio Vaccine

    PubMed Central

    Cherkasova, E. A.; Yakovenko, M. L.; Rezapkin, G. V.; Korotkova, E. A.; Ivanova, O. E.; Eremeeva, T. P.; Krasnoproshina, L. I.; Romanenkova, N. I.; Rozaeva, N. R.; Sirota, L.; Agol, V. I.; Chumakov, K. M.

    2005-01-01

    Sabin strains used in the manufacture of oral polio vaccine (OPV) replicate in the human organism and can give rise to vaccine-derived polioviruses. The increased neurovirulence of vaccine derivatives has been known since the beginning of OPV use, but their ability to establish circulation in communities has been recognized only recently during the latest stages of the polio eradication campaign. This important observation called for studies of their emergence and evolution as well as extensive surveillance to determine the scope of this phenomenon. Here, we present the results of a study of vaccine-derived isolates from an immunocompromised poliomyelitis patient, the contacts, and the local sewage. All isolates were identified as closely related and slightly evolved vaccine derivatives with a recombinant type 2/type 1 genome. The strains also shared several amino acid substitutions including a mutation in the VP1 protein that was previously shown to be associated with the loss of attenuation. Another mutation in the VP3 protein resulted in altered immunological properties of the isolates, possibly facilitating virus spread in immunized populations. The patterns and rates of the accumulation of synonymous mutations in isolates collected from the patient over the extended period of excretion suggest either a substantially nonuniform rate of mutagenesis throughout the genome, or, more likely, the strains may have been intratypic recombinants between coevolving derivatives with different degrees of divergence from the vaccine parent. This study provides insight into the early stages of the establishment of circulation by runaway vaccine strains. PMID:15613335

  7. National choices related to inactivated poliovirus vaccine, innovation and the endgame of global polio eradication.

    PubMed

    Thompson, Kimberly M; Duintjer Tebbens, Radboud J

    2014-02-01

    Achieving the goal of a world free of poliomyelitis still requires significant effort. Although polio immunization represents a mature area, the polio endgame will require new tools and strategies, particularly as national and global health leaders coordinate the cessation of all three serotypes of oral poliovirus vaccine and increasingly adopt inactivated poliovirus vaccine (IPV). Poliovirus epidemiology and the global options for managing polioviruses continue to evolve, along with our understanding and appreciation of the resources needed and the risks that require management. Based on insights from modeling, we offer some perspective on the current status of plans and opportunities to achieve and maintain a world free of wild polioviruses and to successfully implement oral poliovirus vaccine cessation. IPV costs and potential wastage will represent an important consideration for national policy makers. Innovations may reduce future IPV costs, but the world urgently needs lower-cost IPV options.

  8. Poliovirus trafficking toward central nervous system via human poliovirus receptor-dependent and -independent pathway

    PubMed Central

    Ohka, Seii; Nihei, Coh-ichi; Yamazaki, Manabu; Nomoto, Akio

    2012-01-01

    In humans, paralytic poliomyelitis results from the invasion of the central nervous system (CNS) by circulating poliovirus (PV) via the blood–brain barrier (BBB). After the virus enters the CNS, it replicates in neurons, especially in motor neurons, inducing the cell death that causes paralytic poliomyelitis. Along with this route of dissemination, neural pathway has been reported in humans, monkeys, and PV-sensitive human PV receptor (hPVR/CD155)-transgenic (Tg) mice. We demonstrated that a fast retrograde axonal transport process is required for PV dissemination through the sciatic nerve of hPVR-Tg mice and that intramuscularly inoculated PV causes paralysis in a hPVR-dependent manner. We also showed that hPVR-independent axonal transport of PV exists in hPVR-Tg and non-Tg mice, indicating that several different pathways for PV axonal transport exist in these mice. Circulating PV after intravenous inoculation in mice cross the BBB at a high rate in a hPVR-independent manner. We will implicate an involvement of a new possible receptor for PV to permeate the BBB based on our recent findings. PMID:22529845

  9. Isolation and Characterization of Vaccine-Derived Polioviruses, Relevance for the Global Polio Eradication Initiative.

    PubMed

    Xu, Wenbo; Zhang, Yong

    2016-01-01

    Stool specimens were collected from children with acute flaccid paralysis (AFP) and their contacts, and viral isolation was performed according to standard procedures. If the specimens tested positive for poliovirus, then intratypic differentiation (ITD) methods were performed on the viral isolates to determine whether the poliovirus isolates were wild or of vaccine origin, these include a poliovirus diagnostic ITD real-time PCR method and a vaccine-derived poliovirus (VDPV) screening real-time PCR method.Viral RNA was extracted from the poliovirus isolates by using the QIAamp Mini Viral RNA Extraction Kit (Qiagen) and was used for RT-PCR amplification by the standard method. The entire VP1 region of the poliovirus isolates was amplified by RT-PCR with primers that flanked the VP1-coding region. After purification of the PCR products by the QIAquick Gel Extraction Kit (Qiagen), the amplicons were bidirectionally sequenced with the ABI PRISM 3130 Genetic Analyzer (Applied Biosystems). A neurovirulence test of polioviruses isolates was carried out using PVR-Tg21 mice that expressed the human poliovirus receptor (CD155). And the temperature sensitivities of polioviruses isolates were assayed on monolayer RD cells in 24-well plates as described.

  10. Poliovirus Mutants Resistant to Neutralization with Soluble Cell Receptors

    NASA Astrophysics Data System (ADS)

    Kaplan, Gerardo; Peters, David; Racaniello, Vincent R.

    1990-12-01

    Poliovirus mutants resistant to neutralization with soluble cellular receptor were isolated. Replication of soluble receptor-resistant (srr) mutants was blocked by a monoclonal antibody directed against the HeLa cell receptor for poliovirus, indicating that the mutants use this receptor to enter cells. The srr mutants showed reduced binding to HeLa cells and cell membranes. However, the reduced binding phenotype did not have a major impact on viral replication, as judged by plaque size and one-step growth curves. These results suggest that the use of soluble receptors as antiviral agents could lead to the selection of neutralization-resistant mutants that are able to bind cell surface receptors, replicate, and cause disease.

  11. Poliovirus RNA synthesis in vitro: structural elements and antibody inhibition

    SciTech Connect

    Semler, B.L.; Hanecak, R.; Dorner, L.F.; Anderson, C.W.; Wimmer, E.

    1983-01-01

    The poliovirus RNA polymerase complex has been analyzed by immunoautoradiography using antibody probes derived from purified replicase (P3) region viral polypeptides. Antibody preparations made against the polio RNA polymerase, P3-4b, detected a previously unreported cellular protein that copurifies with the RNA polymerase. An IgG fraction purified from rabbit antiserum to polypeptide P3-2, a precursor fo the RNA polymerase, specifically inhibits poliovirus RNA synthesis in vitro. The authors have also immunoprecipitated a 60,000-dalton protein (P3-4a) with antiserum to protein P3-4b and have determined the precise genomic map position of this protein by automated Edman degradation. Protein P3-4a originates by cleavage of the RNA polymerase precursor at a glutamine-glucine amino acid pair not previously reported to be a viral cleavage site.

  12. Chlorine resistance of poliovirus isolants recovered from drinking water.

    PubMed Central

    Shaffer, P T; Metcalf, T G; Sproul, O J

    1980-01-01

    Poliovirus 1 isolants were recovered from finished drinking water produced by a modern, well-operated water treatment plant. These waters contained free chlorine residuals in excess of 1 mg/liter. The chlorine inactivation of purified high-titer preparations of two such isolants was compared with the inactivation behavior of two stock strains of poliovirus 1, LSc and Mahoney. The surviving fraction of virus derived from the two natural isolants was shown to be orders of magnitude greater than that of the standard strains. These results raise the question whether indirect drinking water standards based on free chlorine residuals are adequate public health measures, or whether direct standards based on virus determinations might be necessary. Images PMID:6257162

  13. Inactivation of poliovirus by formaldehyde: theoretical and practical aspects.

    PubMed

    GARD, S

    1957-01-01

    Since formaldehyde, either alone or in combination with other inactivating agents, is at present used in the production of all so-called "killed" poliovirus vaccines, a thorough knowledge of the kinetics of the reaction between the chemical agent and the virus, and of the mechanisms involved, is of great practical importance. In this paper the problem is discussed against the background of present knowledge of the structure of the virus and the chemical nature of the action of formaldehyde.

  14. 78 FR 55214 - Annual Marine Events in the Eighth Coast Guard District, Sabine River; Orange, TX

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-10

    ... SECURITY Coast Guard 33 CFR Part 100 Annual Marine Events in the Eighth Coast Guard District, Sabine River; Orange, TX AGENCY: Coast Guard, DHS. ACTION: Notice of enforcement of regulation. SUMMARY: The Coast.... Coast Guard Marine Safety Unit Port Arthur, TX; telephone 409-719-5086, email scott.k.whalen@uscg.mil...

  15. 77 FR 47519 - Annual Marine Events in the Eighth Coast Guard District, Sabine River; Orange, TX

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-09

    ... SECURITY Coast Guard 33 CFR Part 100 Annual Marine Events in the Eighth Coast Guard District, Sabine River; Orange, TX AGENCY: Coast Guard, DHS. ACTION: Notice of enforcement of regulation. SUMMARY: The Coast..., call or email Mr. Scott Whalen. U.S. Coast Guard Marine Safety Unit Port Arthur, TX; telephone 409-719...

  16. Time of travel of solutes in the Sabine River basin, Texas, August-November 1996

    USGS Publications Warehouse

    Raines, Timothy H.

    1997-01-01

    The U.S. Geological Survey (USGS), in cooperation with the Sabine River Authority, did a time-of-travel study in the Sabine River Basin during low flow from August to November 1996. The study was done to provide accurate estimates of the time-of-travel and dispersion characteristics for solutes during low flow in a 1.8-mile (mi) reach of Grace Creek, a 23.9-mi reach of the mainstem Sabine River, a 3.4-mi reach of Hawkins Creek, and a 1.9-mi reach of Rocky Creek. This report explains the approach and documents the results of the study. The results of the study will be used by the Texas Natural Resource Conservation Commission in a water-quality model to determine waste-load allocation in Segment 0505 of the Sabine River Basin. The time-of-travel and dispersion characteristics also provide useful information on the probable behavior of soluble contaminants that might be introduced into the streams measured in this study.

  17. Photometry and models of selected main belt asteroids. III. 283 Emma, 665 Sabine, and 690 Wratislavia

    NASA Astrophysics Data System (ADS)

    Michałowski, T.; Kaasalainen, M.; Polińska, M.; Marciniak, A.; Kwiatkowski, T.; Kryszczyńska, A.; Velichko, F. P.

    2006-11-01

    Photometric observations of 283 Emma (1998, 2000, 2001, 2004), 665 Sabine (1998, 1999, 2001, 2004, 2005), and 690 Wratislavia (1998, 2000, 2004, 2005-2006) carried out on 44 nights at two observatories are presented. Using all available lightcurves, the spin vectors, senses of rotation, and shape models for these three asteroids have been determined.

  18. 78 FR 44934 - Sabine Pass Liquefaction, LLC; Application for Long-Term Authorization To Export Liquefied...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-25

    ... from the Sabine Pass LNG Terminal in Cameron Parish, Louisiana, both to: (i) Any nation that currently... vaporization terminal in Cameron, Parish, Louisiana (Liquefaction Project). On April 16, 2012, the Federal... Cameron Parish, Louisiana, to: (i) Any country with which the United States currently has, or in the...

  19. 33 CFR 165.806 - Sabine Neches Waterway, Texas-regulated navigation area.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 2 2014-07-01 2014-07-01 false Sabine Neches Waterway, Texas-regulated navigation area. 165.806 Section 165.806 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) PORTS AND WATERWAYS SAFETY REGULATED NAVIGATION AREAS AND LIMITED...

  20. 33 CFR 165.806 - Sabine Neches Waterway, Texas-regulated navigation area.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 2 2012-07-01 2012-07-01 false Sabine Neches Waterway, Texas-regulated navigation area. 165.806 Section 165.806 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) PORTS AND WATERWAYS SAFETY REGULATED NAVIGATION AREAS AND LIMITED...

  1. 33 CFR 165.806 - Sabine Neches Waterway, Texas-regulated navigation area.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 2 2011-07-01 2011-07-01 false Sabine Neches Waterway, Texas-regulated navigation area. 165.806 Section 165.806 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) PORTS AND WATERWAYS SAFETY REGULATED NAVIGATION AREAS AND LIMITED...

  2. 33 CFR 165.806 - Sabine Neches Waterway, Texas-regulated navigation area.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 2 2013-07-01 2013-07-01 false Sabine Neches Waterway, Texas-regulated navigation area. 165.806 Section 165.806 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) PORTS AND WATERWAYS SAFETY REGULATED NAVIGATION AREAS AND LIMITED...

  3. Identification of the initiation site of poliovirus polyprotein synthesis

    SciTech Connect

    Dorner, A.J.; Dorner, L.F.; Larsen, G.R.; Wimmer, E.; Anderson, C.W.

    1982-06-01

    The complete nucleotide sequence of poliovirus RNA has a long open reading frame capable of encoding the precursor polyprotein NCVPOO. The first AUG codon in this reading frame is located 743 nucleotides from the 5' end of the RNA and is preceded by eight AUG codons in all three reading frames. Because all proteins that map at the amino terminus of the polyprotein (P1-1a, VPO, and VP4) are blocked at their amino termini and previous studies of ribosome binding have been inconclusive, direct identification of the initiation site of protein synthesis was difficult. We separated and identified all of the tryptic peptides of capsid protein VP4 and correlated these peptides with the amino acid sequence predicted to follow the AUG codon at nucleotide 743. Our data indicate that VP4 begins with a blocked glycine that is encoded immediately after the AUG codon at nucleotide 743. An S1 nuclease analysis of poliovirus mRNA failed to reveal a splice in the 5' region. We concluded that synthesis of poliovirus polyprotein is initiated at nucleotide 743, the first AUG codon in the long open reading frame.

  4. Expanding knowledge of P3 proteins in the poliovirus lifecycle

    PubMed Central

    Cameron, Craig E; Oh, Hyung Suk; Moustafa, Ibrahim M

    2010-01-01

    Poliovirus is the most extensively studied member of the order Picornavirales, which contains numerous medical, veterinary and agricultural pathogens. The picornavirus genome encodes a single polyprotein that is divided into three regions: P1, P2 and P3. P3 proteins are known to participate more directly in genome replication, for example by containing the viral RNA-dependent RNA polymerase (RdRp or 3Dpol), among several other proteins and enzymes. We will review recent data that provide new insight into the structure, function and mechanism of P3 proteins and their complexes, which are required for initiation of genome replication. Replication of poliovirus genomes occurs within macromolecular complexes, containing viral RNA, viral proteins and host-cell membranes, collectively referred to as replication complexes. P2 proteins clearly contribute to interactions with the host cell that are required for virus multiplication, including formation of replication complexes. We will discuss recent data that suggest a role for P3 proteins in formation of replication complexes. Among the least understood steps of the poliovirus lifecycle is encapsidation of genomic RNA. We will also describe data that suggest a role for P3 proteins in this step. PMID:20521933

  5. Methods for the Quality Control of Inactivated Poliovirus Vaccines.

    PubMed

    Wilton, Thomas

    2016-01-01

    Inactivated poliovirus vaccine (IPV) plays an instrumental role in the Global Poliovirus Eradication Initiative (GPEI). The quality of IPV is controlled by assessment of the potency of vaccine batches. The potency of IPV can be assessed by both in vivo and in vitro methods. In vitro potency assessment is based upon the assessment of the quantity of the D-Antigen (D-Ag) units in an IPV. The D-Ag unit is used as a measure of potency as it is largely expressed on native infectious virions and is the protective immunogen. The most commonly used in vitro test is the indirect ELISA which is used to ensure consistency throughout production.A range of in vivo assays have been developed in monkeys, chicks, guinea pigs, mice, and rats to assess the potency of IPV. All are based on assessment of the neutralizing antibody titer within the sera of the respective animal model. The rat potency test has become the favored in vivo potency test as it shows minimal variation between laboratories and the antibody patterns of rats and humans are similar. With the development of transgenic mice expressing the human poliovirus receptor, immunization-challenge tests have been developed to assess the potency of IPVs. This chapter describes in detail the methodology of these three laboratory tests to assess the quality of IPVs.

  6. Neurovirulence of Type 1 Polioviruses Isolated from Sewage in Japan

    PubMed Central

    Horie, Hitoshi; Yoshida, Hiromu; Matsuura, Kumiko; Miyazawa, Miwako; Ota, Yoshihiro; Nakayama, Takashi; Doi, Yutaka; Hashizume, So

    2002-01-01

    Sixteen type 1 poliovirus strains were isolated from a sewage disposal plant located downstream of the Oyabe River in Japan between October 1993 and September 1995. The isolates were intratypically differentiated as vaccine-derived strains. Neutralizing antigenicity analysis with monoclonal antibodies and estimation of neurovirulence by mutant analysis by PCR and restriction enzyme cleavage (MAPREC) were performed for 13 type 1 strains of these isolates. The isolates were classified into three groups. Group I (five strains) had a variant type of antigenicity and neurovirulent phenotype. Group II (four strains) had the vaccine type of antigenicity and neurovirulent phenotype. Group III (four strains) had the vaccine type of antigenicity and an attenuated phenotype. Furthermore, it was demonstrated that the virulent isolates were neutralized by human sera obtained after oral poliomyelitis vaccine (OPV) administration, and the sera of rats immunized with inactivated poliovirus vaccine. Although vaccination was effective against virulent polioviruses, virulent viruses will continue to exist in the environment as long as OPV is in use. PMID:11772619

  7. Functional oligomerization of poliovirus RNA-dependent RNA polymerase.

    PubMed Central

    Pata, J D; Schultz, S C; Kirkegaard, K

    1995-01-01

    Using a hairpin primer/template RNA derived from sequences present at the 3' end of the poliovirus genome, we investigated the RNA-binding and elongation activities of highly purified poliovirus 3D polymerase. We found that surprisingly high polymerase concentrations were required for efficient template utilization. Binding of template RNAs appeared to be the primary determinant of efficient utilization because binding and elongation activities correlated closely. Using a three-filter binding assay, polymerase binding to RNA was found to be highly cooperative with respect to polymerase concentration. At pH 5.5, where binding was most cooperative, a Hill coefficient of 5 was obtained, indicating that several polymerase molecules interact to retain the 110-nt RNA in a filter-bound complex. Chemical crosslinking with glutaraldehyde demonstrated physical polymerase-polymerase interactions, supporting the cooperative binding data. We propose a model in which poliovirus 3D polymerase functions both as a catalytic polymerase and as a cooperative single-stranded RNA-binding protein during RNA-dependent RNA synthesis. Images FIGURE 1 FIGURE 2 FIGURE 5 FIGURE 6 FIGURE 8 PMID:7489508

  8. Assessment of cell culture and polymerase chain reaction procedures for the detection of polioviruses in wastewater.

    PubMed Central

    Grabow, W. O.; Botma, K. L.; de Villiers, J. C.; Clay, C. G.; Erasmus, B.

    1999-01-01

    WHO considers that environmental surveillance for wild-type polioviruses is potentially important for surveillance for acute flaccid paralysis as a means of confirming eradication of poliomyelitis. The present study investigated methods for detecting polioviruses in a variety of water environments in South Africa. Most polioviruses were isolated on L20B mouse cells, which, however, were not selective: 16 reoviruses and 8 enteroviruses, apparently animal strains, were also isolated on these cells. Vaccine strains of polioviruses were isolated from surface waters during and shortly after two rounds of mass vaccination of children in an informal settlement where there was no sewerage. The results demonstrated the feasibility of poliovirus surveillance in such settlements. It was also evident that neither poliovirus vaccine strains nor other viruses were likely to interfere significantly with the detection of wild-type polioviruses. Optimal isolation of polioviruses was accomplished by parallel inoculation of L20B mouse cells and at least the PLC/PRF/5 human liver and buffalo green monkey (BGM) kidney cell lines. Analysis of cell cultures using the polymerase chain reaction revealed that 319 test samples contained at least 263 human enteroviruses that failed to produce a cytopathogenic effect. This type of analysis thus significantly increased the sensitivity of enterovirus detection. PMID:10680244

  9. Impact of inactivated poliovirus vaccine on mucosal immunity: implications for the polio eradication endgame

    PubMed Central

    Parker, Edward PK; Molodecky, Natalie A; Pons-Salort, Margarita; O’Reilly, Kathleen M; Grassly, Nicholas C

    2015-01-01

    The polio eradication endgame aims to bring transmission of all polioviruses to a halt. To achieve this aim, it is essential to block viral replication in individuals via induction of a robust mucosal immune response. Although it has long been recognized that inactivated poliovirus vaccine (IPV) is incapable of inducing a strong mucosal response on its own, it has recently become clear that IPV may boost immunity in the intestinal mucosa among individuals previously immunized with oral poliovirus vaccine. Indeed, mucosal protection appears to be stronger following a booster dose of IPV than oral poliovirus vaccine, especially in older children. Here, we review the available evidence regarding the impact of IPV on mucosal immunity, and consider the implications of this evidence for the polio eradication endgame. We conclude that the implementation of IPV in both routine and supplementary immunization activities has the potential to play a key role in halting poliovirus transmission, and thereby hasten the eradication of polio. PMID:26159938

  10. Patients with Primary Immunodeficiencies Are a Reservoir of Poliovirus and a Risk to Polio Eradication

    PubMed Central

    Aghamohammadi, Asghar; Abolhassani, Hassan; Kutukculer, Necil; Wassilak, Steve G.; Pallansch, Mark A.; Kluglein, Samantha; Quinn, Jessica; Sutter, Roland W.; Wang, Xiaochuan; Sanal, Ozden; Latysheva, Tatiana; Ikinciogullari, Aydan; Bernatowska, Ewa; Tuzankina, Irina A.; Costa-Carvalho, Beatriz T.; Franco, Jose Luis; Somech, Raz; Karakoc-Aydiner, Elif; Singh, Surjit; Bezrodnik, Liliana; Espinosa-Rosales, Francisco J.; Shcherbina, Anna; Lau, Yu-Lung; Nonoyama, Shigeaki; Modell, Fred; Modell, Vicki; Ozen, Ahmet; Barbouche, Mohamed-Ridha; McKinlay, Mark A.

    2017-01-01

    Immunodeficiency-associated vaccine-derived polioviruses (iVDPVs) have been isolated from primary immunodeficiency (PID) patients exposed to oral poliovirus vaccine (OPV). Patients may excrete poliovirus strains for months or years; the excreted viruses are frequently highly divergent from the parental OPV and have been shown to be as neurovirulent as wild virus. Thus, these patients represent a potential reservoir for transmission of neurovirulent polioviruses in the post-eradication era. In support of WHO recommendations to better estimate the prevalence of poliovirus excreters among PIDs and characterize genetic evolution of these strains, 635 patients including 570 with primary antibody deficiencies and 65 combined immunodeficiencies were studied from 13 OPV-using countries. Two stool samples were collected over 4 days, tested for enterovirus, and the poliovirus positive samples were sequenced. Thirteen patients (2%) excreted polioviruses, most for less than 2 months following identification of infection. Five (0.8%) were classified as iVDPVs (only in combined immunodeficiencies and mostly poliovirus serotype 2). Non-polio enteroviruses were detected in 30 patients (4.7%). Patients with combined immunodeficiencies had increased risk of delayed poliovirus clearance compared to primary antibody deficiencies. Usually, iVDPV was detected in subjects with combined immunodeficiencies in a short period of time after OPV exposure, most for less than 6 months. Surveillance for poliovirus excretion among PID patients should be reinforced until polio eradication is certified and the use of OPV is stopped. Survival rates among PID patients are improving in lower and middle income countries, and iVDPV excreters are identified more frequently. Antivirals or enhanced immunotherapies presently in development represent the only potential means to manage the treatment of prolonged excreters and the risk they present to the polio endgame. PMID:28952612

  11. The past and present role of the Sabin-Feldman dye test in the serodiagnosis of toxoplasmosis.

    PubMed Central

    Reiter-Owona, I.; Petersen, E.; Joynson, D.; Aspöck, H.; Dardé, M. L.; Disko, R.; Dreazen, O.; Dumon, H.; Grillo, R.; Gross, U.; Hayde, M.; Holliman, R.; Ho-Yen, D. O.; Janitschke, K.; Jenum, P. A.; Naser, K.; Olszewski, M.; Thulliez, P.; Seitz, H. M.

    1999-01-01

    The dye test for the detection of Toxoplasma-specific antibodies was first described by Sabin and Feldman 50 years ago. The test is highly specific and sensitive and considerable information is available on the development and persistence of dye test antibodies after primary Toxoplasma infection. However, the test uses live Toxoplasma gondii and is now only employed in a few laboratories. It is still the reference method for the serodiagnosis of toxoplasmosis, and a multicentre study comparing dye test results between different laboratories was much needed. We report in this article the results of a multicentre evaluation of the test involving nineteen laboratories in eight countries. The study revealed overall satisfactory standardization between the laboratories, but there were differences in the test protocols, the use of reference/standard preparations and the interpretation of results. There is still no agreement on the level of dye test values which reflect infection with the parasite, and conversion from titres to international units (IUs) did not improve standardization. However, the results indicated that a value of > 4 IU or a titre of 1:16 met the definition of positivity of most participants. We recommend that the dye test be retained as a reference method and that interlaboratory standardization be improved by the use of a common protocol and the expression of results in titres. PMID:10612889

  12. Inactivation by bromine of single poliovirus particles in water.

    PubMed Central

    Floyd, R; Johnson, J D; Sharp, D G

    1976-01-01

    Quantitative electron microscopy shows that Freon-extracted poliovirus, velocity banded in a sucrose gradient, contains over 95% single particles. This well-dispersed virus reacts quite rapidly with bromine in turbulent flowing water, losing plaque titer at the rate of one log10 unit in 10s at pH 7, 2 C, and at a bromine concentration of 2.2 muM. At 10 and 20 C the rate of disinfection (log10 plaque-forming units per second) is faster, and at both temperatures it increases in approximately linear fashion with increasing bromine concentration. At 2 C such a linear relationship is not observed. Images PMID:11745

  13. Isolation of viruses from sewage, with special regard to poliovirus

    PubMed Central

    Böttiger, Margareta

    1978-01-01

    This report concerns experiments to isolate different viruses from sewage. Using a special cell-line from Utrecht, derived from human amniotic cells, it was possible to isolate poliovirus selectively when antisera against six types of coxsackievirus B were added to the tissue culture. The method was tested in connexion with the epidemiological investigation of a case of poliomyelitis in Sweden in 1977. It rapidly demonstrated that the virus implicated was present in all neighbouring sewage plants, indicating a wide distribution of the virus in the area. PMID:216501

  14. Discharge measurement in tidally affected channels during a hydrographic estuarine survey of Sabine Lake, Texas

    USGS Publications Warehouse

    Dunn, David D.; Solis, R.S.; Ockerman, D.J.

    1997-01-01

    A hydrographic survey of Sabine Lake, a broad, shallow estuary lying on the Texas-Louisiana border, was conducted in June 1996 to help address questions relating to potential environmental effects of future water demands in Texas. The use of a variety of new instruments in this study is one means by which automation is improving efficiency and effectiveness of these efforts by increasing the quality and quantity of data collected.

  15. Achieving high seroprevalence against polioviruses in Sri Lanka--results from a serological survey, 2014.

    PubMed

    Gamage, Deepa; Palihawadana, Paba; Mach, Ondrej; Weldon, William C; Oberste, Steven M; Sutter, Roland W

    2015-12-01

    The immunization program in Sri Lanka consistently reaches >90% coverage with oral poliovirus vaccines (OPV), and no polio supplementary vaccination campaigns have been conducted since 2003. We evaluated serological protection against polioviruses in children. A cross-sectional community-based survey was performed in three districts of Sri Lanka (Colombo, Badulla, and Killinochi). Randomly selected children in four age groups (9-11 months, 3-4 years, 7-9 years, and 15 years) were tested for poliovirus neutralizing antibodies. All 400 enrolled children completed the study. The proportion of seropositive children for poliovirus Type 1 and Type 2 was >95% for all age groups; for poliovirus Type 3 it was 95%, 90%, 77%, and 75% in the respective age groups. The vaccination coverage in our sample based on vaccination cards or parental recall was >90% in all age groups. Most Sri Lankan children are serologically protected against polioviruses through routine immunization only. This seroprevalence survey provided baseline data prior to the anticipated addition of inactivated poliovirus vaccine (IPV) into the Sri Lankan immunization program and the switch from trivalent OPV (tOPV) to bivalent OPV (bOPV).

  16. Cross-neutralizing human anti-poliovirus antibodies bind the recognition site for cellular receptor

    PubMed Central

    Chen, Zhaochun; Fischer, Elizabeth R.; Kouiavskaia, Diana; Hansen, Bryan T.; Ludtke, Steven J.; Bidzhieva, Bella; Makiya, Michelle; Agulto, Liane; Purcell, Robert H.; Chumakov, Konstantin

    2013-01-01

    Most structural information about poliovirus interaction with neutralizing antibodies was obtained in the 1980s in studies of mouse monoclonal antibodies. Recently we have isolated a number of human/chimpanzee anti-poliovirus antibodies and demonstrated that one of them, MAb A12, could neutralize polioviruses of both serotypes 1 and 2. This communication presents data on isolation of an additional cross-neutralizing antibody (F12) and identification of a previously unknown epitope on the surface of poliovirus virions. Epitope mapping was performed by sequencing of antibody-resistant mutants and by cryo-EM of complexes of virions with Fab fragments. The results have demonstrated that both cross-neutralizing antibodies bind the site located at the bottom of the canyon surrounding the fivefold axis of symmetry that was previously shown to interact with cellular poliovirus receptor CD155. However, the same antibody binds to serotypes 1 and 2 through different specific interactions. It was also shown to interact with type 3 poliovirus, albeit with about 10-fold lower affinity, insufficient for effective neutralization. Antibody interaction with the binding site of the cellular receptor may explain its broad reactivity and suggest that further screening or antibody engineering could lead to a universal antibody capable of neutralizing all three serotypes of poliovirus. PMID:24277851

  17. Risks of paralytic disease due to wild or vaccine-derived poliovirus after eradication.

    PubMed

    Tebbens, Radboud J Duintjer; Pallansch, Mark A; Kew, Olen M; Cáceres, Victor M; Jafari, Hamid; Cochi, Stephen L; Sutter, Roland W; Aylward, R Bruce; Thompson, Kimberly M

    2006-12-01

    After the global eradication of wild polioviruses, the risk of paralytic poliomyelitis from polioviruses will still exist and require active management. Possible reintroductions of poliovirus that can spread rapidly in unprotected populations present challenges to policymakers. For example, at least one outbreak will likely occur due to circulation of a neurovirulent vaccine-derived poliovirus after discontinuation of oral poliovirus vaccine and also could possibly result from the escape of poliovirus from a laboratory or vaccine production facility or from an intentional act. In addition, continued vaccination with oral poliovirus vaccines would result in the continued occurrence of vaccine-associated paralytic poliomyelitis. The likelihood and impacts of reintroductions in the form of poliomyelitis outbreaks depend on the policy decisions and on the size and characteristics of the vulnerable population, which change over time. A plan for managing these risks must begin with an attempt to characterize and quantify them as a function of time. This article attempts to comprehensively characterize the risks, synthesize the existing data available for modeling them, and present quantitative risk estimates that can provide a starting point for informing policy decisions.

  18. RNA binding and replication by the poliovirus RNA polymerase

    SciTech Connect

    Oberste, M.S.

    1988-01-01

    RNA binding and RNA synthesis by the poliovirus RNA-dependent RNA polymerase were studied in vitro using purified polymerase. Templates for binding and RNA synthesis studies were natural RNAs, homopolymeric RNAs, or subgenomic poliovirus-specific RNAs synthesized in vitro from cDNA clones using SP6 or T7 RNA polymerases. The binding of the purified polymerase to poliovirion and other RNAs was studied using a protein-RNA nitrocellulose filter binding assay. A cellular poly(A)-binding protein was found in the viral polymerase preparations, but was easily separated from the polymerase by chromatography on poly(A) Sepharose. The binding of purified polymerase to {sup 32}P-labeled ribohomopolymeric RNAs was examined, and the order of binding observed was poly(G) >>> poly(U) > poly(C) > poly(A). The K{sub a} for polymerase binding to poliovirion RNA and to a full-length negative strand transcript was about 1 {times} 10{sup 9} M{sup {minus}1}. The polymerase binds to a subgenomic RNAs which contain the 3{prime} end of the genome with a K{sub a} similar to that for virion RNA, but binds less well to 18S rRNA, globin mRNA, and subgenomic RNAs which lack portions of the 3{prime} noncoding region.

  19. Cleavage sites within the poliovirus capsid protein precursors

    SciTech Connect

    Larsen, G.R.; Anderson, C.W.; Dorner, A.J.; Semler, B.L.; Wimmer, E.

    1982-01-01

    Partial amino-terminal sequence analysis was performed on radiolabeled poliovirus capsid proteins VP1, VP2, and VP3. A computer-assisted comparison of the amino acid sequences obtained with that predicted by the nucleotide sequence of the poliovirus genome allows assignment of the amino terminus of each capsid protein to a unique position within the virus polyprotein. Sequence analysis of trypsin-digested VP4, which has a blocked amino terminus, demonstrates that VP4 is encoded at or very near to the amino terminus of the polyprotein. The gene order of the capsid proteins is VP4-VP2-VP3-VP1. Cleavage of VP0 to VP4 and VP2 is shown to occur between asparagine and serine, whereas the cleavages that separate VP2/VP3 and VP3/VP1 occur between glutamine and glycine residues. This finding supports the hypothesis that the cleavage of VP0, which occurs during virion morphogenesis, is distinct from the cleavages that separate functional regions of the polyprotein.

  20. Conserved aspartic acid 233 and alanine 231 are not required for poliovirus polymerase function in replicons

    PubMed Central

    Freistadt, Marion S; Eberle, Karen E

    2007-01-01

    Nucleic acid polymerases have similar structures and motifs. The function of an aspartic acid (conserved in all classes of nucleic acid polymerases) in motif A remains poorly understood in RNA-dependent RNA polymerases. We mutated this residue to alanine in a poliovirus replicon. The resulting mutant could still replicate, although at a reduced level. In addition, mutation A231C (also in motif A) yielded high levels of replication. Taken together these results show that poliovirus polymerase conserved residues D233 and A231 are not essential to poliovirus replicon function. PMID:17352827

  1. Monensin and nigericin prevent the inhibition of host translation by poliovirus, without affecting p220 cleavage.

    PubMed Central

    Irurzun, A; Sánchez-Palomino, S; Novoa, I; Carrasco, L

    1995-01-01

    Addition of monensin or nigericin after poliovirus entry into HeLa cells prevents the inhibition of host protein synthesis by poliovirus. The infected cells continue to synthesize cellular proteins at control levels for at least 8 h after infection in the presence of the ionophore. Cleavage of p220 (gamma subunit of eukaryotic initiation factor 4 [eIF-4 gamma]), a component of the translation initiation factor eIF-4F, occurs to the same extent in poliovirus-infected cells whether or not they are treated with monensin. Two hours after infection there is no detectable intact p220, but the cells continue to translate cellular mRNAs for several hours at levels similar to those in uninfected cells. Nigericin or monensin prevented the arrest of host translation at all the multiplicities of poliovirus infection tested. At high multiplicities of infection, an unprecedented situation was found: cells synthesized poliovirus and cellular proteins simultaneously. Superinfection of vesicular stomatitis virus-infected HeLa cells with poliovirus led to a profound inhibition of vesicular stomatitis virus protein synthesis, while nigericin partially prevented this blockade. Drastic inhibition of translation also took place in influenza virus-infected Vero cells treated with nigericin and infected with poliovirus. These findings suggest that the translation of newly synthesized mRNAs is dependent on the integrity of p220, while ongoing cellular protein synthesis does not require an intact p220. The target of ionophore action during the poliovirus life cycle was also investigated. Addition of nigericin at any time postinfection profoundly blocked the synthesis of virus RNA, whereas viral protein synthesis was not affected if nigericin was added at 4 h postinfection. These results agree well with previous findings indicating that inhibitors of phospholipid synthesis or vesicular traffic interfere with poliovirus genome replication. Therefore, the action of nigericin on the vesicular

  2. Monensin and nigericin prevent the inhibition of host translation by poliovirus, without affecting p220 cleavage.

    PubMed

    Irurzun, A; Sánchez-Palomino, S; Novoa, I; Carrasco, L

    1995-12-01

    Addition of monensin or nigericin after poliovirus entry into HeLa cells prevents the inhibition of host protein synthesis by poliovirus. The infected cells continue to synthesize cellular proteins at control levels for at least 8 h after infection in the presence of the ionophore. Cleavage of p220 (gamma subunit of eukaryotic initiation factor 4 [eIF-4 gamma]), a component of the translation initiation factor eIF-4F, occurs to the same extent in poliovirus-infected cells whether or not they are treated with monensin. Two hours after infection there is no detectable intact p220, but the cells continue to translate cellular mRNAs for several hours at levels similar to those in uninfected cells. Nigericin or monensin prevented the arrest of host translation at all the multiplicities of poliovirus infection tested. At high multiplicities of infection, an unprecedented situation was found: cells synthesized poliovirus and cellular proteins simultaneously. Superinfection of vesicular stomatitis virus-infected HeLa cells with poliovirus led to a profound inhibition of vesicular stomatitis virus protein synthesis, while nigericin partially prevented this blockade. Drastic inhibition of translation also took place in influenza virus-infected Vero cells treated with nigericin and infected with poliovirus. These findings suggest that the translation of newly synthesized mRNAs is dependent on the integrity of p220, while ongoing cellular protein synthesis does not require an intact p220. The target of ionophore action during the poliovirus life cycle was also investigated. Addition of nigericin at any time postinfection profoundly blocked the synthesis of virus RNA, whereas viral protein synthesis was not affected if nigericin was added at 4 h postinfection. These results agree well with previous findings indicating that inhibitors of phospholipid synthesis or vesicular traffic interfere with poliovirus genome replication. Therefore, the action of nigericin on the vesicular

  3. 33 CFR 334.790 - Sabine River at Orange, Tex.; restricted area in vicinity of the Naval and Marine Corps Reserve...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 3 2011-07-01 2011-07-01 false Sabine River at Orange, Tex... RESTRICTED AREA REGULATIONS § 334.790 Sabine River at Orange, Tex.; restricted area in vicinity of the Naval.... Government or those duly authorized by the Commanding Officer, Naval and Marine Corps Reserve Center, Orange...

  4. 33 CFR 334.790 - Sabine River at Orange, Tex.; restricted area in vicinity of the Naval and Marine Corps Reserve...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 3 2012-07-01 2012-07-01 false Sabine River at Orange, Tex... RESTRICTED AREA REGULATIONS § 334.790 Sabine River at Orange, Tex.; restricted area in vicinity of the Naval.... Government or those duly authorized by the Commanding Officer, Naval and Marine Corps Reserve Center, Orange...

  5. 33 CFR 334.790 - Sabine River at Orange, Tex.; restricted area in vicinity of the Naval and Marine Corps Reserve...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 3 2014-07-01 2014-07-01 false Sabine River at Orange, Tex... RESTRICTED AREA REGULATIONS § 334.790 Sabine River at Orange, Tex.; restricted area in vicinity of the Naval.... Government or those duly authorized by the Commanding Officer, Naval and Marine Corps Reserve Center, Orange...

  6. 33 CFR 334.790 - Sabine River at Orange, Tex.; restricted area in vicinity of the Naval and Marine Corps Reserve...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 3 2010-07-01 2010-07-01 false Sabine River at Orange, Tex... RESTRICTED AREA REGULATIONS § 334.790 Sabine River at Orange, Tex.; restricted area in vicinity of the Naval.... Government or those duly authorized by the Commanding Officer, Naval and Marine Corps Reserve Center, Orange...

  7. 33 CFR 334.790 - Sabine River at Orange, Tex.; restricted area in vicinity of the Naval and Marine Corps Reserve...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 3 2013-07-01 2013-07-01 false Sabine River at Orange, Tex... RESTRICTED AREA REGULATIONS § 334.790 Sabine River at Orange, Tex.; restricted area in vicinity of the Naval.... Government or those duly authorized by the Commanding Officer, Naval and Marine Corps Reserve Center, Orange...

  8. Oral and Inactivated Poliovirus Vaccines in the Newborn: A review

    PubMed Central

    Mateen, Farrah J.; Shinohara, Russell T.; Sutter, Roland W.

    2015-01-01

    Background Oral poliovirus vaccine (OPV) remains the vaccine-of-choice for routine immunization and supplemental immunization activities (SIAs) to eradicate poliomyelitis globally. Recent data from India suggested lowerthanexpected immunogenicity of an OPV birth dose, prompting a review of the immunogenicity of OPV or inactivated poliovirus vaccine (IPV) when administered at birth. Methods We evaluated the seroconversion and reported adverse events among infants given a single birth dose (given ≤7 days of life) of OPV or IPV through a systematic review of published articles and conference abstracts from 1959-2011 in any language found on PubMed, Google Scholar, or reference lists of selected articles. Results 25 articles from 13 countries published between1959 and 2011 documented seroconversion rates in newborns following an OPV dose given within the first seven days of life. There were 10 studies that measured seroconversion rates between 4 and 8 weeks of a single birth dose of TOPV, using an umbilical cord blood draw at the time of birth to establish baseline antibody levels. The percentage of newborns who seroconverted at 8 weeks range 6-42% for poliovirus type 1, 2-63% for type 2, and 1-35% for type 3). For mOPV type 1, seroconversion ranged from 10-76%; mOPV type 3, the range was 12-58%; and for the one study reporting bOPV, it was 20% for type 1 and 7% for type 3. There were four studies of IPV in newborns with a seroconversion rate of 8-100% for serotype 1, 15-100% for serotype 2, and 15-94% for serotype 3, measured at 4-6 weeks of life. No serious adverse events related to newborn OPV or IPV dosing were reported, including no cases of acute flaccid paralysis. Conclusions There is great variability of the immunogenicity of a birth dose of OPV for reasons largely unknown. Our review confirms the utility of a birth dose of OPV, particularly in countries where early induction of polio immunity is imperative. IPV has higher seroconversion rates in newborns and

  9. Poliovirus Polymerase Leu420 Facilitates RNA Recombination and Ribavirin Resistance

    PubMed Central

    Kempf, Brian J.; Peersen, Olve B.

    2016-01-01

    ABSTRACT RNA recombination is important in the formation of picornavirus species groups and the ongoing evolution of viruses within species groups. In this study, we examined the structure and function of poliovirus polymerase, 3Dpol, as it relates to RNA recombination. Recombination occurs when nascent RNA products exchange one viral RNA template for another during RNA replication. Because recombination is a natural aspect of picornavirus replication, we hypothesized that some features of 3Dpol may exist, in part, to facilitate RNA recombination. Furthermore, we reasoned that alanine substitution mutations that disrupt 3Dpol-RNA interactions within the polymerase elongation complex might increase and/or decrease the magnitudes of recombination. We found that an L420A mutation in 3Dpol decreased the frequency of RNA recombination, whereas alanine substitutions at other sites in 3Dpol increased the frequency of recombination. The 3Dpol Leu420 side chain interacts with a ribose in the nascent RNA product 3 nucleotides from the active site of the polymerase. Notably, the L420A mutation that reduced recombination also rendered the virus more susceptible to inhibition by ribavirin, coincident with the accumulation of ribavirin-induced G→A and C→U mutations in viral RNA. We conclude that 3Dpol Leu420 is critically important for RNA recombination and that RNA recombination contributes to ribavirin resistance. IMPORTANCE Recombination contributes to the formation of picornavirus species groups and the emergence of circulating vaccine-derived polioviruses (cVDPVs). The recombinant viruses that arise in nature are occasionally more fit than either parental strain, especially when the two partners in recombination are closely related, i.e., members of characteristic species groups, such as enterovirus species groups A to H or rhinovirus species groups A to C. Our study shows that RNA recombination requires conserved features of the viral polymerase. Furthermore, a

  10. Poliovirus immunity in newly resettled adult refugees in Idaho, United States of America.

    PubMed

    Roscoe, Clay; Gilles, Ryan; Reed, Alex J; Messerschmidt, Matt; Kinney, Rebecca

    2015-06-12

    In the United States, vaccines have eliminated wild poliovirus (WPV) infection, though resettling refugees may lack immunity and importation of WPV remains a concern. A cross-sectional survey was performed to determine the prevalence of poliovirus immunity in adult refugees resettling in Boise, Idaho, U.S.A.; immunity was evaluated using two definitions: serotypes 1, 2 and 3 positive, or serotypes 1 and 3 positive. This survey evaluated 795 adult refugees between August 2010 and November 2012. Poliovirus immunity in adults >18 years was 55.3% for serotypes 1, 2 and 3 combined, and 60% for serotypes 1 and 3 only. This study demonstrated a WPV immunity rate of <60% in a recently resettled adult refugee population in the United States, reinforcing the need to ensure poliovirus immunity in all newly arrived adult refugees, either by expanding pre-departure immunization or by screening for immunity at resettlement and vaccinating when indicated. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Comparison between adsorption of poliovirus and rotavirus by aluminum hydroxide and activated sludge flocs.

    PubMed Central

    Farrah, S R; Goyal, S M; Gerba, C P; Conklin, R H; Smith, E M

    1978-01-01

    Adsorption of poliovirus and rotavirus by aluminum hydroxide and activated sludge flocs was studied. Both aluminum hydroxide and activated sludge flocs adsorbed greater amounts of poliovirus than rotavirus. Aluminum hydroxide flocs reduced the titer of poliovirus in tap water by 3 log10, but they only reduced the titer of a simian rotovirus (SA-11) in tap water by 1 log10 or less and did not noticeably reduce the number of human rotavirus particles present in a dilute stool suspension. Activated sludge flocs reduced the titer of added poliovirus by 0.7 to 1.8 log10 and reduced the titer of SA-11 by 0.5 log10 or less. These studies indicate that a basic difference in the adsorptive behavior of enteroviruses and rotaviruses exists and that water and wastewater treatment processes that are highly effective in removal of enteroviruses may not be as effective in removing other viral groups such as rotaviruses. PMID:205173

  12. The Alpha/Beta Interferon Response Controls Tissue Tropism and Pathogenicity of Poliovirus

    PubMed Central

    Ida-Hosonuma, Miki; Iwasaki, Takuya; Yoshikawa, Tomoki; Nagata, Noriyo; Sato, Yuko; Sata, Tetsutaro; Yoneyama, Mitsutoshi; Fujita, Takashi; Taya, Choji; Yonekawa, Hiromichi; Koike, Satoshi

    2005-01-01

    Poliovirus selectively replicates in neurons in the spinal cord and brainstem, although poliovirus receptor (PVR) expression is observed in both the target and nontarget tissues in humans and transgenic mice expressing human PVR (PVR-transgenic mice). We assessed the role of alpha/beta interferon (IFN) in determining tissue tropism by comparing the pathogenesis of the virulent Mahoney strain in PVR-transgenic mice and PVR-transgenic mice deficient in the alpha/beta IFN receptor gene (PVR-transgenic/Ifnar knockout mice). PVR-transgenic/Ifnar knockout mice showed increased susceptibility to poliovirus. After intravenous inoculation, severe lesions positive for the poliovirus antigen were detected in the liver, spleen, and pancreas in addition to the central nervous system. These results suggest that the alpha/beta IFN system plays an important role in determining tissue tropism by protecting nontarget tissues that are potentially susceptible to infection. We subsequently examined the expression of IFN and IFN-stimulated genes (ISGs) in the PVR-transgenic mice. In the nontarget tissues, ISGs were expressed even in the noninfected state, and the expression level increased soon after poliovirus infection. On the contrary, in the target tissues, ISG expression was low in the noninfected state and sufficient response after poliovirus infection was not observed. The results suggest that the unequal IFN response is one of the important determinants for the differential susceptibility of tissues to poliovirus. We consider that poliovirus replication was observed in the nontarget tissues of PVR-transgenic/Ifnar knockout mice because the IFN response was null in all tissues. PMID:15767446

  13. A monoclonal antibody that blocks poliovirus attachment recognizes the lymphocyte homing receptor CD44.

    PubMed Central

    Shepley, M P; Racaniello, V R

    1994-01-01

    A monoclonal antibody, AF3, was previously shown to specifically inhibit poliovirus binding to HeLa cells and to detect a 100-kDa glycoprotein only in cell lines and tissues permissive for poliovirus infection. These results suggested that the 100-kDa protein may be involved in the pathogenesis of poliomyelitis and the cellular function of the poliovirus receptor site. To study further the role of the 100-kDa protein in poliovirus attachment, immunoaffinity purification, amino acid sequencing, and cDNA cloning were undertaken. The results demonstrate that antibody AF3 reacts with the lymphocyte homing receptor CD44, a multifunctional cell surface glycoprotein involved in the homing of circulating lymphocytes to lymph nodes and the modulation of lymphocyte adhesion and activation. Antibody AF3 reacts with a subset of CD44 molecules (AF3CD44H), which appears to be a small fraction of the heterogeneously glycosylated CD44 molecules expressed on hematopoietic and nonhematopoietic cells. Anti-CD44 monoclonal antibodies, previously reported to induce CD44-mediated modulation of lymphocyte activation and adhesion, compete with 125I-AF3 in binding assays, demonstrating functional overlap among the epitopes. The anti-CD44 monoclonal antibody A3D8, which binds to a greater molecular weight range of CD44 than does AF3, inhibits poliovirus binding to a similar degree. CD44 does not act as a poliovirus receptor, since CD44-expressing mouse L-cell transformants did not bind poliovirus. The poliovirus receptor and AF3CD44H may be noncovalently associated, or they may interact through the cytoskeleton or signal transduction pathways. Images PMID:7508992

  14. Analysis of mutations in oral poliovirus vaccine by hybridization with generic oligonucleotide microchips.

    SciTech Connect

    Proudnikov, D.; Kirillov, E.; Chumakov, K.; Donion, J.; Rezapkin, G.; Mirzabekov, A.; Biochip Technology Center; Engelhardt Inst. of Molecular Biology; Center for Biologics Evaluation and Research

    2000-01-01

    This paper describes use of a new technology of hybridization with a micro-array of immobilized oligonucleotides for detection and quantification of neurovirulent mutants in Oral Poliovirus Vaccine (OPV). We used a micro-array consisting of three-dimensional gel-elements containing all possible hexamers (total of 4096 probes). Hybridization of fluorescently labelled viral cDNA samples with such microchips resulted in a pattern of spots that was registered and quantified by a computer-linked CCD camera, so that the sequence of the original cDNA could be deduced. The method could reliably identify single point mutations, since each of them affected fluorescence intensity of 12 micro-array elements. Micro-array hybridization of DNA mixtures with varying contents of point mutants demonstrated that the method can detect as little as 10% of revertants in a population of vaccine virus. This new technology should be useful for quality control of live viral vaccines, as well as for other applications requiring identification and quantification of point mutations.

  15. Poliovirus Studies during the Endgame of the Polio Eradication Program.

    PubMed

    Arita, Minetaro

    2017-01-24

    Since the beginning of Global Polio Eradication Initiative in 1988, poliomyelitis cases caused by wild poliovirus (PV) have been drastically reduced, with only 74 cases reported in 2 endemic countries in 2015. The current limited PV transmission suggests that we are in the endgame of the polio eradication program. However, specific challenges have emerged in the endgame, including tight budget, switching of the vaccines, and changes in biorisk management of PV. To overcome these challenges, several PV studies have been implemented in the eradication program. Some of the responses to the emerging challenges in the polio endgame might be valuable in other infectious diseases eradication programs. Here, I will review challenges that confront the polio eradication program and current research to address these challenges.

  16. Can post-eradication laboratory containment of wild polioviruses be achieved?

    PubMed Central

    Dowdle, Walter R.; Gary, Howard E.; Sanders, Raymond; van Loon, Anton M.

    2002-01-01

    The purpose of containment is to prevent reintroduction of wild polioviruses from laboratories into polio-free communities. In order to achieve global commitment to laboratory containment the rationale should be clear and compelling; the biosafety levels should be justified by the risks; and the objectives should be realistic. Absolute containment can never be assured. Questions of intentional or unintentional non-compliance can never be wholly eliminated. Effective laboratory containment is, however, a realistic goal. Prevention of virus transmission through contaminated laboratory materials is addressed by WHO standards for biosafety. The principal challenge is to prevent transmission through unrecognized infectious laboratory workers. Such transmission is possible only if the following conditions occur: infectious and potentially infectious materials carrying wild poliovirus are present in the laboratory concerned; a laboratory operation exposes a worker to poliovirus; a worker is susceptible to an infection that results in the shedding of poliovirus; and the community is susceptible to poliovirus infections. At present it is difficult to envisage the elimination of any of these conditions. However, the risks of the first three can be greatly reduced so as to create a formidable barrier against poliovirus transmission to the community. Final biosafety recommendations must await post-eradication immunization policies adopted by the international community. PMID:12075368

  17. The Multifaceted Poliovirus 2A Protease: Regulation of Gene Expression by Picornavirus Proteases

    PubMed Central

    Castelló, Alfredo; Álvarez, Enrique; Carrasco, Luis

    2011-01-01

    After entry into animal cells, most viruses hijack essential components involved in gene expression. This is the case of poliovirus, which abrogates cellular translation soon after virus internalization. Abrogation is achieved by cleavage of both eIF4GI and eIF4GII by the viral protease 2A. Apart from the interference of poliovirus with cellular protein synthesis, other gene expression steps such as RNA and protein trafficking between nucleus and cytoplasm are also altered. Poliovirus 2Apro is capable of hydrolyzing components of the nuclear pore, thus preventing an efficient antiviral response by the host cell. Here, we compare in detail poliovirus 2Apro with other viral proteins (from picornaviruses and unrelated families) as regard to their activity on key host factors that control gene expression. It is possible that future analyses to determine the cellular proteins targeted by 2Apro will uncover other cellular functions ablated by poliovirus infection. Further understanding of the cellular proteins hydrolyzed by 2Apro will add further insight into the molecular mechanism by which poliovirus and other viruses interact with the host cell. PMID:21541224

  18. Wild and vaccine-derived poliovirus circulation, and implications for polio eradication.

    PubMed

    Lopalco, P L

    2017-02-01

    Polio cases due to wild virus are reported by only three countries in the world. Poliovirus type 2 has been globally eradicated and the last detection of poliovirus type 3 dates to November 2012. Poliovirus type 1 remains the only circulating wild strain; between January and September 2016 it caused 26 cases (nine in Afghanistan, 14 in Pakistan, three in Nigeria). The use of oral polio vaccine (OPV) has been the key to success in the eradication effort. However, paradoxically, moving towards global polio eradication, the burden caused by vaccine-derived polioviruses (VDPVs) becomes increasingly important. In this paper circulation of both wild virus and VDPVs is reviewed and implications for the polio eradication endgame are discussed. Between April and May 2016 OPV2 cessation has been implemented globally, in a coordinated switch from trivalent OPV to bivalent OPV. In order to decrease the risk for cVDPV2 re-emergence inactivated polio vaccine (IPV) has been introduced in the routine vaccine schedule of all countries. The likelihood of re-emergence of cVDPVs should markedly decrease with time after OPV cessation, but silent circulation of polioviruses cannot be ruled out even a long time after cessation. For this reason, immunity levels against polioviruses should be kept as high as possible in the population by the use of IPV, and both clinical and environmental surveillance should be maintained at a high level.

  19. Contribution of Environmental Surveillance Toward Interruption of Poliovirus Transmission in Nigeria, 2012–2015

    PubMed Central

    Johnson Muluh, Ticha; Hamisu, Abdullahi Walla; Craig, Kehinde; Mkanda, Pascal; Andrew, Etsano; Adeniji, Johnson; Akande, Adefunke; Musa, Audu; Ayodeji, Isiaka; Nicksy, Gumede; Banda, Richard; Tegegne, Sisay G.; Nsubuga, Peter; Oyetunji, Ajiboye; Diop, Ousmane; Vaz, Rui G.; Muhammad, Ado J. G.

    2016-01-01

    Background. Cases of paralysis caused by poliovirus have decreased by >99% since the 1988 World Health Assembly's resolution to eradicate polio. The World Health Organization identified environmental surveillance (ES) of poliovirus in the poliomyelitis eradication strategic plan as an activity that can complement acute flaccid paralysis (AFP) surveillance. This article summarizes key public health interventions that followed the isolation of polioviruses from ES between 2012 and 2015. Methods. The grap method was used to collect 1.75 L of raw flowing sewage every 2–4 weeks. Once collected, samples were shipped at 4°C to a polio laboratory for concentration. ES data were then used to guide program implementation. Results. From 2012 to 2015, ES reported 97 circulating vaccine-derived polioviruses (cVDPV2) and 14 wild polioviruses. In 2014 alone, 54 cVDPV type 2 cases and 1 WPV type 1 case were reported. In Sokoto State, 58 cases of AFP were found from a search of 9426 households. A total of 2 252 059 inactivated polio vaccine and 2 460 124 oral polio vaccine doses were administered to children aged <5 year in Borno and Yobe states. Conclusions. This article is among the first from Africa that relates ES findings to key public health interventions (mass immunization campaigns, inactivated polio vaccine introduction, and strengthening of AFP surveillance) that have contributed to the interruption of poliovirus transmission in Nigeria. PMID:26908747

  20. Framework for evaluating the risks of paralytic poliomyelitis after global interruption of wild poliovirus transmission.

    PubMed Central

    Aylward, R. Bruce; Cochi, Stephen L.

    2004-01-01

    With the interruption of wild poliovirus transmission globally, the need for new policies to deal with the post-certification era will rapidly arise. New policies will be required in four areas: detection and notification of circulating polioviruses; biocontainment of wild, vaccine-derived and attenuated strains of poliovirus; vaccine stockpiles and response mechanisms; and routine immunization against polioviruses. A common understanding of the potential risks of paralytic poliomyelitis in the post-certification period is essential to the development of these policies. Since 2000, there has been increasing international consensus that the risks of paralytic poliomyelitis in the post-certification era fall into two categories: those due to the continued use of the oral poliovirus vaccine (OPV) and those due to future improper handling of wild polioviruses. The specific risks within both categories have now been defined, and an understanding of the frequency and potential burden of disease associated with each is rapidly improving. This knowledge and clarity have provided a framework that is already proving valuable for identifying research priorities and discussing potential policy options with national authorities. However, this framework must be regarded as a dynamic tool, requiring regular updating as additional information on these risks becomes available through further scientific research, programmatic work, and policy decisions. PMID:15106299

  1. THE FORMATION AND PROPERTIES OF POLIOVIRUS-NEUTRALIZING ANTIBODY

    PubMed Central

    Svehag, Sven-Eric; Mandel, Benjamin

    1964-01-01

    Rapid formation of poliovirus-neutralizing antibody was observed in the rabbit. 19S type antibody was detectable 8 to 12 hours following a single intravenous virus injection and the induction period was of the order of 4 to 5 hours or less. The production of 7S antibody had a longer lag phase (1½ to 2 days) and it was formed at slower rate. The observed rate of early 19S and 7S antibody formation as well as the peak titers of the two antibodies were antigen dose dependent. Normal rabbit sera showed low neutralizing activity to several viral antigens in a sensitive assay system. Following intravenous inoculation of poliovirus either transitory (⩽ 1 month) or enduring (¾ to 1½ year) antibody formation resulted depending upon the dose of antigen employed. In transitory responses, which could be induced by a single small antigen dose, only 19S antibody was demonstrable and there was an abrupt cessation of antibody synthesis on day 4 or 5. In enduring responses, both 19S and 7S antibody were formed and the minimum antigen dose required for initiation of such a response was equal to the dose needed for induction of 7S antibody formation. Thus, enduring antibody formation was an all-or-none phenomenon depending upon whether or not 7S antibody formation was induced. The antigen dose requirement for induction of 7S antibody was much higher (by 50-fold or more) than that for 19S antibody. This allowed a determination of antigen dose regions, within which predictably transitory (19S) or enduring (19S + 7S) antibody formation was obtained. These pronounced differences in antigen dose requirement for induction and kinetics of formation of 19S and 7S antibody suggest that the same cells do not participate in the formation of the two antibodies. PMID:14113113

  2. Myristoylation is important at multiple stages in poliovirus assembly.

    PubMed Central

    Moscufo, N; Simons, J; Chow, M

    1991-01-01

    The N-terminal glycine of the VP4 capsid subunit of poliovirus is covalently modified with myristic acid (C14 saturated fatty acid). To investigate the function of VP4 myristoylation in poliovirus replication, amino acid substitutions were placed within the myristoylation consensus sequence at the alanine residue (4003A) adjacent to the N-terminal glycine by using site-directed mutagenesis methods. Mutants which replace the alanine residue with a small hydrophobic residue such as leucine, valine, or glycine displayed normal levels of myristoylation and normal growth kinetics. Replacement with the polar amino acid histidine (4003A.H) also resulted in a level of myristoylation comparable to that of the wild type. However, replacement of the alanine residue with aspartic acid (4003A.D) caused a dramatic reduction (about 40 to 60%) in myristoylation levels of the VP4 precursors (P1 and VP0). In contrast, no differences in modification levels were found in either VP0 and VP4 proteins isolated from mature mutant virions, indicating that myristoylation is required for assembly of the infectious virion. The myristoylation levels of the VP0 proteins found in capsid assembly intermediates indicate that there is a strong but not absolute preference for myristoyl-modified subunits during pentamer formation. Complete myristoylation was observed in mature virions but not in assembly intermediates, indicating that there is a selection for myristoyl-modified subunits during stable RNA encapsidation to form the mature virus particle. In addition, even though mutant infectious virions are fully modified, the severe reduction in specific infectivity of both 4003A.D and 4003A.H purified viruses indicates that the amino acid residue adjacent to the N-terminal glycine apparently has an additional role early during viral infection and that mutations at this position induce pleiotropic effects. Images PMID:1850017

  3. Translating Ribosomes Inhibit Poliovirus Negative-Strand RNA Synthesis

    PubMed Central

    Barton, David J.; Morasco, B. Joan; Flanegan, James B.

    1999-01-01

    Poliovirus has a single-stranded RNA genome of positive polarity that serves two essential functions at the start of the viral replication cycle in infected cells. First, it is translated to synthesize viral proteins and, second, it is copied by the viral polymerase to synthesize negative-strand RNA. We investigated these two reactions by using HeLa S10 in vitro translation-RNA replication reactions. Preinitiation RNA replication complexes were isolated from these reactions and then used to measure the sequential synthesis of negative- and positive-strand RNAs in the presence of different protein synthesis inhibitors. Puromycin was found to stimulate RNA replication overall. In contrast, RNA replication was inhibited by diphtheria toxin, cycloheximide, anisomycin, and ricin A chain. Dose-response experiments showed that precisely the same concentration of a specific drug was required to inhibit protein synthesis and to either stimulate or inhibit RNA replication. This suggested that the ability of these drugs to affect RNA replication was linked to their ability to alter the normal clearance of translating ribosomes from the input viral RNA. Consistent with this idea was the finding that the protein synthesis inhibitors had no measurable effect on positive-strand synthesis in normal RNA replication complexes. In marked contrast, negative-strand synthesis was stimulated by puromycin and was inhibited by cycloheximide. Puromycin causes polypeptide chain termination and induces the dissociation of polyribosomes from mRNA. Cycloheximide and other inhibitors of polypeptide chain elongation “freeze” ribosomes on mRNA and prevent the normal clearance of ribosomes from viral RNA templates. Therefore, it appears that the poliovirus polymerase was not able to dislodge translating ribosomes from viral RNA templates and mediate the switch from translation to negative-strand synthesis. Instead, the initiation of negative-strand synthesis appears to be coordinately regulated

  4. Poliovirus excretion among persons with primary immune deficiency disorders: summary of a seven-country study series.

    PubMed

    Li, Li; Ivanova, Olga; Driss, Nadia; Tiongco-Recto, Marysia; da Silva, Rajiva; Shahmahmoodi, Shohreh; Sazzad, Hossain M S; Mach, Ondrej; Kahn, Anna-Lea; Sutter, Roland W

    2014-11-01

    Persons with primary immune deficiency disorders (PID), especially those disorders affecting the B-cell system, are at substantially increased risk of paralytic poliomyelitis and can excrete poliovirus chronically. However, the risk of prolonged or chronic excretion is not well characterized in developing countries. We present a summary of a country study series on poliovirus excretion among PID cases. Cases with PID from participating institutions were enrolled during the first year and after obtaining informed consent were tested for polioviruses in stool samples. Those cases excreting poliovirus were followed on a monthly basis during the second year until 2 negative stool samples were obtained. A total of 562 cases were enrolled in Bangladesh, China, Iran, Philippines, Russia, Sri Lanka, and Tunisia during 2008-2013. Of these, 17 (3%) shed poliovirus, including 2 cases with immunodeficient vaccine-derived poliovirus. Poliovirus was detected in a single sample from 5/17 (29%) cases. One case excreted for more than 6 months. None of the cases developed paralysis during the study period. Chronic polioviruses excretion remains a rare event even among individuals with PID. Nevertheless, because these individuals were not paralyzed they would have been missed by current surveillance; therefore, surveillance for polioviruses among PID should be established. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  5. Antigen sparing with adjuvanted inactivated polio vaccine based on Sabin strains

    PubMed Central

    Westdijk, Janny; Koedam, Patrick; Barro, Mario; Steil, Benjamin P.; Collin, Nicolas; Vedvick, Thomas S.; Bakker, Wilfried A.M.; van der Ley, Peter; Kersten, Gideon

    2013-01-01

    Six different adjuvants, each in combination with inactivated polio vaccine (IPV) produced with attenuated Sabin strains (sIPV), were evaluated for their ability to enhance virus neutralizing antibody titers (VNTs) in the rat potency model. The increase of VNTs was on average 3-, 15-, 24-fold with adjuvants after one immunization (serotype 1, 2, and 3, respectively). Also after a boost immunization the VNTs of adjuvanted sIPV were on average another 7- 20- 27 times higher than after two inoculations of sIPV without adjuvant. The results indicate that it is feasible to increase the potency of inactivated polio vaccines by using adjuvants. PMID:23313617

  6. An evaluation of the sensitivity of acute flaccid paralysis surveillance for poliovirus infection in Australia

    PubMed Central

    2009-01-01

    Background World Health Organization (WHO) targets for acute flaccid paralysis (AFP) surveillance, including the notification of a minimum rate of AFP among children, are used to assess the adequacy of AFP surveillance for the detection of poliovirus infection. Sensitive surveillance for poliovirus infection in both developed and developing countries is essential to support global disease eradication efforts. We applied recently developed methods for the quantitative evaluation of disease surveillance systems to evaluate the sensitivity of AFP surveillance for poliovirus infection in Australia. Methods A scenario tree model which accounted for administrative region, age, population immunity, the likelihood of AFP, and the probability of notification and stool sampling was used to assess the sensitivity of AFP surveillance for wild poliovirus infection among children aged less than 15 years in Australia. The analysis was based on historical surveillance data collected between 2000 and 2005. We used a surveillance time period of one month, and evaluated the ability of the surveillance system to detect poliovirus infection at a prevalence of 1 case per 100 000 persons and 1 case per million persons. Results There was considerable variation in the sensitivity of AFP surveillance for poliovirus infection among Australian States and Territories. The estimated median sensitivity of AFP surveillance in Australia among children aged less than 15 years was 8.2% per month at a prevalence of 1 case per 100,000 population, and 0.9% per month at a prevalence of 1 case per million population. The probability that Australia is free from poliovirus infection given negative surveillance findings following 5 years of continuous surveillance was 96.9% at a prevalence of 1 case per 100,000 persons and 56.5% at a prevalence of 1 case per million persons. Conclusion Given the ongoing risk of poliovirus importation prior to global eradication, long term surveillance is required to provide

  7. Inactivation of Poliovirus Type 1 by the Kelly-Purdy Ultraviolet Seawater Treatment Unit1

    PubMed Central

    Hill, William F.; Hamblet, Frederick E.; Benton, William H.

    1969-01-01

    Three experiments were conducted to determine the effect of ultraviolet (UV) radiation on poliovirus-contaminated seawater. In two of the experiments, the effectiveness of the Kelly-Purdy UV Seawater Treatment Unit to inactivate poliovirus type 1 (T1) suspended in continuously flowing seawater was determined. In experiment 1, the observed survival ratio of poliovirus T1 was 2.3 × 10-4 (99.98% reduction) in 15.7 sec. No virus was detected (<0.2 plaque-forming unit/ml) in 20.6 seconds. The calculated half-life value was 1.29 sec. In experiment 2, the observed survival ratio of poliovirus T1 was 5.9 × 10-4 (99.94% reduction) in 11.7 sec. No virus was detected in 15.7 sec. The calculated half-life value was 1.37 sec. In experiment 3, a laboratory-controlled UV experiment designed to closely simulate the geometry of the continuously flowing seawater system, the observed survival ratios of poliovirus T1 were 9.7 × 10-3 (99.03% reduction) and 3.6 × 10-4 (99.96% reduction) in 15 and 30 sec, respectively; the calculated half-life value was 2.38 sec. A statistically significant difference was found between the inactivation rates of poliovirus T1 in the two test systems. This rate difference was attributed primarily to UV dosage and stirring effects. The data indicated that UV radiation effectively inactivated poliovirus T1 in flowing seawater. These results validate the efficacy of the Kelly-Purdy UV Seawater Treatment Unit for use in commercial depuration systems. Images PMID:4304572

  8. Inactivation of poliovirus type 1 by the Kelly-Purdy ultraviolet seawater treatment unit.

    PubMed

    Hill, W F; Hamblet, F E; Benton, W H

    1969-01-01

    Three experiments were conducted to determine the effect of ultraviolet (UV) radiation on poliovirus-contaminated seawater. In two of the experiments, the effectiveness of the Kelly-Purdy UV Seawater Treatment Unit to inactivate poliovirus type 1 (T(1)) suspended in continuously flowing seawater was determined. In experiment 1, the observed survival ratio of poliovirus T(1) was 2.3 x 10(-4) (99.98% reduction) in 15.7 sec. No virus was detected (<0.2 plaque-forming unit/ml) in 20.6 seconds. The calculated half-life value was 1.29 sec. In experiment 2, the observed survival ratio of poliovirus T(1) was 5.9 x 10(-4) (99.94% reduction) in 11.7 sec. No virus was detected in 15.7 sec. The calculated half-life value was 1.37 sec. In experiment 3, a laboratory-controlled UV experiment designed to closely simulate the geometry of the continuously flowing seawater system, the observed survival ratios of poliovirus T(1) were 9.7 x 10(-3) (99.03% reduction) and 3.6 x 10(-4) (99.96% reduction) in 15 and 30 sec, respectively; the calculated half-life value was 2.38 sec. A statistically significant difference was found between the inactivation rates of poliovirus T(1) in the two test systems. This rate difference was attributed primarily to UV dosage and stirring effects. The data indicated that UV radiation effectively inactivated poliovirus T(1) in flowing seawater. These results validate the efficacy of the Kelly-Purdy UV Seawater Treatment Unit for use in commercial depuration systems.

  9. Seroprevalence of poliovirus antibodies in the Kansas City metropolitan area, 2012-2013.

    PubMed

    Wallace, Gregory S; Pahud, Barbara A; Weldon, William C; Curns, Aaron T; Oberste, M Steven; Harrison, Christopher J

    2017-04-03

    No indigenous cases of poliomyelitis have occurred in the US since 1979; however the risk of importation persists until global eradication is achieved. The seropositivity rate for different age cohorts with exposures to different poliovirus vaccine types and wild virus in the US are not presently known. A convenience sample was conducted in the Kansas City metropolitan area during 2012-2103 with approximately 100 participants enrolled for each of 5 age cohorts categorized based on vaccine policy changes over time in the US. Immunization records for poliovirus vaccination were required for participants <18 y of age. We evaluated the prevalence of serum antibodies to all 3 poliovirus serotypes. Seroprevalence was evaluated by demographics as well as between polio serotypes. The overall seroprevalence to poliovirus was 90.7%, 94.4%, and 83.3%, for types 1, 2, and 3, respectively. Seroprevalence was high (88.6%-96.2%) for all 3 types of poliovirus for the 6-10 y old age group that was likely to have received a complete schedule of IPV-only vaccination. Children 2-3 y of age, who have not yet completed their full IPV series, had lower seroprevalence compared with all older age groups for types 1 and 2 (p-value <0. 05). Seroprevalence was high for all 3 types of poliovirus in the population surveyed. Seroprevalence for subjects aged 2-3 y was lower than all other age groups for serotypes 1 and 2 highlighting the importance of completing the recommended poliovirus vaccine series with a booster dose at age 4-6 y.

  10. Synthetic virus seeds for improved vaccine safety: Genetic reconstruction of poliovirus seeds for a PER.C6 cell based inactivated poliovirus vaccine.

    PubMed

    Sanders, Barbara P; Edo-Matas, Diana; Papic, Natasa; Schuitemaker, Hanneke; Custers, Jerome H H V

    2015-10-13

    Safety of vaccines can be compromised by contamination with adventitious agents. One potential source of adventitious agents is a vaccine seed, typically derived from historic clinical isolates with poorly defined origins. Here we generated synthetic poliovirus seeds derived from chemically synthesized DNA plasmids encoding the sequence of wild-type poliovirus strains used in marketed inactivated poliovirus vaccines. The synthetic strains were phenotypically identical to wild-type polioviruses as shown by equivalent infectious titers in culture supernatant and antigenic content, even when infection cultures are scaled up to 10-25L bioreactors. Moreover, the synthetic seeds were genetically stable upon extended passaging on the PER.C6 cell culture platform. Use of synthetic seeds produced on the serum-free PER.C6 cell platform ensures a perfectly documented seed history and maximum control over starting materials. It provides an opportunity to maximize vaccine safety which increases the prospect of a vaccine end product that is free from adventitious agents.

  11. A national reference for inactivated polio vaccine derived from Sabin strains in Japan.

    PubMed

    Shirato, Haruko; Someya, Yuichi; Ochiai, Masaki; Horiuchi, Yoshinobu; Takahashi, Motohide; Takeda, Naokazu; Wakabayashi, Kengo; Ouchi, Yasumitsu; Ota, Yoshihiro; Tano, Yoshio; Abe, Shinobu; Yamazaki, Shudo; Wakita, Takaji

    2014-09-08

    As one aspect of its campaign to eradicate poliomyelitis, the World Health Organization (WHO) has encouraged development of the inactivated polio vaccine (IPV) derived from the Sabin strains (sIPV) as an option for an affordable polio vaccine, especially in low-income countries. The Japan Poliomyelitis Research Institute (JPRI) inactivated three serotypes of the Sabin strains and made sIPV preparations, including serotypes 1, 2 and 3 D-antigens in the ratio of 3:100:100. The National Institute of Infectious Diseases, Japan, assessed the immunogenic stability of these sIPV preparations in a rat potency test, according to an evaluation method recommended by the WHO. The immunogenicity of the three serotypes was maintained for at least 4 years when properly stored under -70°C. Based on these data, the sIPV preparations made by JPRI have been approved as national reference vaccines by the Japanese national control authority and used for the quality control of the tetracomponent sIPV-containing diphtheria-tetanus-acellular pertussis combination vaccines that were licensed for a routine polio immunization in Japan. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Quantifying Land Cover Features of the Sabinal River Watershed Using ANFIS

    NASA Astrophysics Data System (ADS)

    Peschel, J. M.; Lacey, R. E.; Haan, P. K.; Kreuter, U. P.

    2002-12-01

    Appraisals of ecological services require quantitative assessments for assigning value to specific contributions. Within ecosystems where resources are limited, such as the semi-arid Edwards Aquifer region of Texas, a quantified interpretation of ecological services change is necessary for effective resource management. The focus of this paper is the development of a supervised neuro-fuzzy sub-pixel classification method to create land cover and land use geographical information datasets. The method has been applied to the Sabinal River watershed, which is located centrally in the Texas counties of Bandera, Real and Uvalde. Through the use of digital elevation model (DEM) data files, an approximate boundary of the Sabinal River watershed was located. Landsat Thematic Mapper (TM) images of the watershed taken in spring and winter of both 1999 and 2000 have been superimposed onto the delineated watershed. Select data from the extracted TM image subset have been coupled with corresponding ground-truth data in order to create an Adaptive Neuro-Fuzzy Inference System (ANFIS) model. After training of the FIS was accomplished, model validation through further ground-truth data comparison was done. Once a reasonable prediction model was developed, the corresponding feature maps were imported into a geographical information system (ArcView) for further analysis.

  13. Pathogenic Events in a Nonhuman Primate Model of Oral Poliovirus Infection Leading to Paralytic Poliomyelitis.

    PubMed

    Shen, Ling; Chen, Crystal Y; Huang, Dan; Wang, Richard; Zhang, Meihong; Qian, Lixia; Zhu, Yanfen; Zhang, Alvin Zhuoran; Yang, Enzhuo; Qaqish, Arwa; Chumakov, Konstantin; Kouiavskaia, Diana; Vignuzzi, Marco; Nathanson, Neal; Macadam, Andrew J; Andino, Raul; Kew, Olen; Xu, Junfa; Chen, Zheng W

    2017-07-15

    Despite a great deal of prior research, the early pathogenic events in natural oral poliovirus infection remain poorly defined. To establish a model for study, we infected 39 macaques by feeding them single high doses of the virulent Mahoney strain of wild type 1 poliovirus. Doses ranging from 10(7) to 10(9) 50% tissue culture infective doses (TCID50) consistently infected all the animals, and many monkeys receiving 10(8) or 10(9) TCID50 developed paralysis. There was no apparent difference in the susceptibilities of the three macaque species (rhesus, cynomolgus, and bonnet) used. Virus excretion in stool and nasopharynges was consistently observed, with occasional viremia, and virus was isolated from tonsils, gut mucosa, and draining lymph nodes. Viral replication proteins were detected in both epithelial and lymphoid cell populations expressing CD155 in the tonsil and intestine, as well as in spinal cord neurons. Necrosis was observed in these three cell types, and viral replication in the tonsil/gut was associated with histopathologic destruction and inflammation. The sustained response of neutralizing antibody correlated temporally with resolution of viremia and termination of virus shedding in oropharynges and feces. For the first time, this model demonstrates that early in the infectious process, poliovirus replication occurs in both epithelial cells (explaining virus shedding in the gastrointestinal tract) and lymphoid/monocytic cells in tonsils and Peyer's patches (explaining viremia), extending previous studies of poliovirus pathogenesis in humans. Because the model recapitulates human poliovirus infection and poliomyelitis, it can be used to study polio pathogenesis and to assess the efficacy of candidate antiviral drugs and new vaccines.IMPORTANCE Early pathogenic events of poliovirus infection remain largely undefined, and there is a lack of animal models mimicking natural oral human infection leading to paralytic poliomyelitis. All 39 macaques fed with

  14. Relaxation of continental lithosphere: An explanation for Late Cretaceous reactivation of the Sabine Uplift of Louisiana-Texas

    NASA Astrophysics Data System (ADS)

    Nunn, Jeffrey A.

    1990-04-01

    With few unconstrained assumptions, a simple quantitative model for flexural isostasy between two crustal blocks of different thickness that subsequently undergoes partial relaxation of accumulated stress can explain reactivation of the Sabine Uplift in the mid-Cretaceous. Thin salt over the Sabine Uplift indicates that it was a positive area in the Middle Jurassic but began to subside during the Late Jurassic. During the Late Jurassic and Early Cretaceous, the Sabine Uplift had no topographic expression and was the center of a large, flat bottomed basin covering most of east Texas and north Louisiana. Reactivation of the Sabine Uplift in the mid-Cretaceous caused a minimum of 150 m of uplift and extensive erosion of Lower Cretaceous rocks. During the Late Cretaceous and Tertiary, the Sabine Uplift resumed subsiding but at a slower rate than the adjacent basins. Since the mid-Cretaceous, the Sabine Uplift has risen more than 1 km relative to the East Texas Basin. We suggest that this structural history is consistent with the following simple quantitative model for flexural isostasy. During formation of the Gulf of Mexico in the Late Triassic-Early Jurassic by rifting and extension of the lithosphere, brittle deformation of the crust created small-scale wavelength of tens of kilometers, lateral variations in crustal thickness. Initially, the newly formed margin was in point-wise Airy isostatic equilibrium. Thus synrift and/or early postrift subsidence was characterized by a series of rift valleys or half grabens separated by uplifts. However, as the margin cooled and contracted, the lithosphere became stronger, and subsequent loading was regionally compensated. Thus postrift subsidence was characterized by a broad regional downwarp. If, at some later point in time, the rigid portion of the lithosphere was weakened or relaxed, then lateral density variations would have been recompensated at shorter wavelengths. Thus areas of little or no crustal extension would have

  15. Innate host barriers to viral trafficking and population diversity: Lessons learned from poliovirus

    PubMed Central

    Pfeiffer, Julie K.

    2011-01-01

    Poliovirus is an error-prone enteric virus spread by the fecal-oral route, and rarely invades the central nervous system (CNS). However, in the rare instances when poliovirus invades the CNS, the resulting damage to motor neurons is striking and often permanent. In the pre-vaccine era, it is likely that most individuals within an epidemic community were infected; however, only 0.5% of infected individuals developed paralytic poliomyelitis. Paralytic poliomyelitis terrified the public and initiated a huge research effort, which was rewarded with two outstanding vaccines. During research to develop the vaccines, many questions were asked: Why did certain people develop paralysis? How does the virus move from the gut to the CNS? What limits viral trafficking to the CNS in the vast majority of infected individuals? Despite over 100 years of poliovirus research, many of these questions remain unanswered. The goal of this chapter is to review our knowledge of how poliovirus moves within and between hosts, how host barriers limit viral movement, how viral population dynamics impact viral fitness and virulence, and to offer hypotheses to explain the rare incidence of paralytic poliovirus disease. PMID:20951871

  16. Environmental surveillance of wild poliovirus circulation in Egypt--balancing between detection sensitivity and workload.

    PubMed

    Hovi, Tapani; Blomqvist, Soile; Nasr, Eman; Burns, Cara C; Sarjakoski, Tarja; Ahmed, Nahed; Savolainen, Carita; Roivainen, Merja; Stenvik, Mirja; Laine, Pia; Barakat, Ibrahim; Wahdan, Mohammed H; Kamel, Faten A; Asghar, Humayun; Pallansch, Mark A; Kew, Olen M; Gary, Howard E; deGourville, Esther M; El Bassioni, Laila

    2005-06-01

    Examination of sewage specimens for poliovirus (environmental surveillance) was adopted as a supplementary tool in the surveillance of poliomyelitis in Egypt. Sewage samples were concentrated about 50-fold using a simple two-phase separation technique, and inoculated in cell cultures in two collaborating laboratories in parallel. All but 9 of the 293 (97%) samples collected from January 2001 to December 2002 contained poliovirus and/or other enteroviruses, with polioviruses being detected in 84% of the samples. The proportion of specimens containing type 1 wild poliovirus (PV1W, the North-East African (NEAF) genotype) was less in 2002 (16%) than in 2001 (57%), and further decreased in 2003. While the overall sensitivity to detect PV1W was similar in the two collaborating laboratories, the specimens scored positive were not identical. Parallel cultures inoculated with aliquots of a given specimen very frequently resulted in isolation of different viruses. Moreover, partial sequence analysis occasionally revealed representatives of different genetic lineages of PV1W in a given specimen. These results emphasize the need to use intensive laboratory analysis to optimise sample sensitivity in environmental poliovirus surveillance, and the difficulties in reproducing the isolation results by simple re-inoculation of samples containing a mixture of different viruses.

  17. Estimated Effect of Inactivated Poliovirus Vaccine Campaigns, Nigeria and Pakistan, January 2014–April 2016

    PubMed Central

    Shirreff, George; Wadood, Mufti Zubair; Vaz, Rui Gama; Sutter, Roland W.

    2017-01-01

    In 2014, inactivated poliovirus vaccine (IPV) campaigns were implemented in Nigeria and Pakistan after clinical trials showed that IPV boosts intestinal immunity in children previously given oral poliovirus vaccine (OPV). We estimated the effect of these campaigns by using surveillance data collected during January 2014–April 2016. In Nigeria, campaigns with IPV and trivalent OPV (tOPV) substantially reduced the incidence of poliomyelitis caused by circulating serotype-2 vaccine–derived poliovirus (incidence rate ratio [IRR] 0.17 for 90 days after vs. 90 days before campaigns, 95% CI 0.04–0.78) and the prevalence of virus in environmental samples (prevalence ratio [PR] 0.16, 95% CI 0.02–1.33). Campaigns with tOPV alone resulted in similar reductions (IRR 0.59, 95% CI 0.18–1.97; PR 0.45, 95% CI 0.21–0.95). In Pakistan, the effect of IPV+tOPV campaigns on wild-type poliovirus was not significant. Results suggest that administration of IPV alongside OPV can decrease poliovirus transmission if high vaccine coverage is achieved. PMID:27861118

  18. Translation without eIF2 promoted by poliovirus 2A protease.

    PubMed

    Redondo, Natalia; Sanz, Miguel Angel; Welnowska, Ewelina; Carrasco, Luis

    2011-01-01

    Poliovirus RNA utilizes eIF2 for the initiation of translation in cell free systems. Remarkably, we now describe that poliovirus translation takes place at late times of infection when eIF2 is inactivated by phosphorylation. By contrast, translation directed by poliovirus RNA is blocked when eIF2 is inactivated at earlier times. Thus, poliovirus RNA translation exhibits a dual mechanism for the initiation of protein synthesis as regards to the requirement for eIF2. Analysis of individual poliovirus non-structural proteins indicates that the presence of 2A(pro) alone is sufficient to provide eIF2 independence for IRES-driven translation. This effect is not observed with a 2A(pro) variant unable to cleave eIF4G. The level of 2A(pro) synthesized in culture cells is crucial for obtaining eIF2 independence. Expression of the N-or C-terminus fragments of eIF4G did not stimulate IRES-driven translation, nor provide eIF2 independence, consistent with the idea that the presence of 2A(pro) at high concentrations is necessary. The finding that 2A(pro) provides eIF2-independent translation opens a new and unsuspected area of research in the field of picornavirus protein synthesis.

  19. Radiation sensitivity of poliovirus, a model for norovirus, inoculated in oyster ( Crassostrea gigas) and culture broth under different conditions

    NASA Astrophysics Data System (ADS)

    Jung, Pil-Mun; Park, Jae Seok; Park, Jin-Gyu; Park, Jae-Nam; Han, In-Jun; Song, Beom-Seok; Choi, Jong-il; Kim, Jae-Hun; Byun, Myung-Woo; Baek, Min; Chung, Young-Jin; Lee, Ju-Woon

    2009-07-01

    Poliovirus is a recognized surrogate for norovirus, pathogen in water and food, due to the structural and genetic similarity. Although radiation sensitivity of poliovirus in water or media had been reported, there has been no research in food model such as shellfish. In this study, oyster ( Crassostrea gigas) was incubated in artificial seawater contaminated with poliovirus, and thus radiation sensitivity of poliovirus was determined in inoculated oyster. The effects of ionizing radiation on the sensitivity of poliovirus were also evaluated under different conditions such as pH (4-7) and salt concentration (1-15%) in culture broth, and temperature during irradiation. The D10 value of poliovirus in PBS buffer, virus culture broth and oyster was determined to 0.46, 2.84 and 2.94 kGy, respectively. The initial plaque forming unit (PFU) of poliovirus in culture broth was slightly decreased as the decrease of pH and the increase of salt concentration, but radiation sensitivity was not affected by pH and salt contents. However, radiation resistance of poliovirus was increased at frozen state. These results provide the basic information for the inactivation of pathogenic virus in foods by using irradiation.

  20. The Practical Consideration of Poliovirus as an Oncolytic Virotherapy

    PubMed Central

    Denniston, Elizabeth; Crewdson, Hannah; Rucinsky, Nicole; Stegman, Andrew; Remenar, Diana; Moio, Katherine; Clark, Brianne; Higginbotham, Alexandra; Keffer, Ross; Brammer, Sarah; Horzempa, Joseph

    2017-01-01

    The inauguration of novel treatment strategies into the clinical setting faces a number of hurdles. In addition to treatment efficacy and safety, acceptance by doctors and patients is paramount to the success of novel therapies. Although viruses are the cause of numerous infectious diseases, these acellular entities have been harnessed over the years to benefit mankind. Recently, a recombinant Poliovirus-Rhinovirus Chimera (PVSRIPO) has shown promise for the treatment of glioblastoma in clinical trials as well as other cancer types in animal models. In this literature review, we discuss the use of PVSRIPO as an oncolytic virotherapy. In addition to being a potential treatment for glioblastoma, this recombinant virus could possibly be used against other cancers because many tumor cells express the PVSRIPO receptor antigens (CD155) and have a limited ability to control viral replication. Moreover, virus-induced immune responses contribute to the efficacy of PVSRIPO. Given the current trajectory of this experimental therapy, the possibility exists that PVSRIPO will soon be a viable treatment option for various cancer types. While many healthcare providers and cancer patients likely welcome this new viral based treatment, history has taught us that some may be skeptical and avoid its use because of the viral composition of this therapy. PMID:28203321

  1. Progress in the development of poliovirus antiviral agents and their essential role in reducing risks that threaten eradication.

    PubMed

    McKinlay, Mark A; Collett, Marc S; Hincks, Jeffrey R; Oberste, M Steven; Pallansch, Mark A; Okayasu, Hiromasa; Sutter, Roland W; Modlin, John F; Dowdle, Walter R

    2014-11-01

    Chronic prolonged excretion of vaccine-derived polioviruses by immunodeficient persons (iVDPV) presents a personal risk of poliomyelitis to the patient as well as a programmatic risk of delayed global eradication. Poliovirus antiviral drugs offer the only mitigation of these risks. Antiviral agents may also have a potential role in the management of accidental exposures and in certain outbreak scenarios. Efforts to discover and develop poliovirus antiviral agents have been ongoing in earnest since the formation in 2007 of the Poliovirus Antivirals Initiative. The most advanced antiviral, pocapavir (V-073), is a capsid inhibitor that has recently demonstrated activity in an oral poliovirus vaccine human challenge model. Additional antiviral candidates with differing mechanisms of action continue to be profiled and evaluated preclinically with the goal of having 2 antivirals available for use in combination to treat iVDPV excreters.

  2. Paralytic poliomyelitis associated with Sabin monovalent and bivalent oral polio vaccines in Hungary.

    PubMed

    Estívariz, Concepción F; Molnár, Zsuzsanna; Venczel, Linda; Kapusinszky, Beatrix; Zingeser, James A; Lipskaya, Galina Y; Kew, Olen M; Berencsi, György; Csohán, Agnes

    2011-08-01

    Historical records of patients with vaccine-associated paralytic poliomyelitis (VAPP) in Hungary during 1961-1981 were reviewed to assess the risk of VAPP after oral polio vaccine (OPV) administration. A confirmed VAPP case was defined as a diagnosis of paralytic poliomyelitis and residual paralysis at 60 days in a patient with an epidemiologic link to the vaccine. Archived poliovirus isolates were retested using polymerase chain reaction and sequencing of the viral protein 1 capsid region. This review confirmed 46 of 47 cases previously reported as VAPP. Three cases originally linked to monovalent OPV (mOPV) 3 and one case linked to mOPV1 presented after administration of bivalent OPV 1 + 3 (bOPV). The adjusted VAPP risk per million doses administered was 0.18 for mOPV1 (2 cases/11.13 million doses), 2.96 for mOPV3 (32 cases/10.81 million doses), and 12.82 for bOPV (5 cases/390,000 doses). Absence of protection from immunization with inactivated poliovirus vaccine or exposure to OPV virus from routine immunization and recent injections could explain the higher relative risk of VAPP in Hungarian children. In polio-endemic areas in which mOPV3 and bOPV are needed to achieve eradication, the higher risk of VAPP would be offset by the high risk of paralysis due to wild poliovirus and higher per-dose efficacy of mOPV3 and bOPV compared with trivalent OPV.

  3. Generation of Infectious Poliovirus with Altered Genetic Information from Cloned cDNA.

    PubMed

    Bujaki, Erika

    2016-01-01

    The effect of specific genetic alterations on virus biology and phenotype can be studied by a great number of available assays. The following method describes the basic protocol to generate infectious poliovirus with altered genetic information from cloned cDNA in cultured cells.The example explained here involves generation of a recombinant poliovirus genome by simply replacing a portion of the 5' noncoding region with a synthetic gene by restriction cloning. The vector containing the full length poliovirus genome and the insert DNA with the known mutation(s) are cleaved for directional cloning, then ligated and transformed into competent bacteria. The recombinant plasmid DNA is then propagated in bacteria and transcribed to RNA in vitro before RNA transfection of cultured cells is performed. Finally, viral particles are recovered from the cell culture.

  4. The recent outbreaks and reemergence of poliovirus in war and conflict-affected areas.

    PubMed

    Akil, Luma; Ahmad, H Anwar

    2016-08-01

    Poliomyelitis is a highly infectious disease caused by poliovirus, which becomes difficult to manage/eradicate in politically unstable areas. The objectives of this study were to determine the movement and management of such polio outbreaks in endemic countries and countries with reoccurring cases of polio and to determine the effect of political instability on polio eradication. In this study, the extent of polio outbreaks was examined and modeled using statistical methodologies and mapped with GIS software. Data on polio cases and immunization were collected for countries with polio cases for the period 2011 to 2014. Weekly data from the Global Polio Eradication Initiative were collected for selected countries. The recent virus origin and current movement was mapped using GIS. Correlations between immunization rates, the Global Peace Index (GPI), and other indicators of a country's political stability with polio outbreaks were determined. Data were analyzed using SAS 9.4 and ArcGIS 10. For several reasons, Pakistan remains highly vulnerable to new incidences of polio (306 cases in 2014). Overall immunization rates showed a steady decline over time in selected countries. Countries with polio cases were shown to have high rates of infant mortality, and their GPI ranked between 2.0 and 3.3; displaced populations, level of violent crime rating, and political instability also were ranked high for several countries. Polio was shown to be high in areas with increased conflict and instability. Displaced populations living in hard-to-reach areas may lack access to proper vaccination and health care. Wars and conflict have also resulted in the reemergence of polio in otherwise polio-free countries. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  5. Primary and booster vaccination with an inactivated poliovirus vaccine (IPV) is immunogenic and well-tolerated in infants and toddlers in China.

    PubMed

    Li, Rongcheng; Li, Chang Gui; Li, Yanping; Liu, Youping; Zhao, Hong; Chen, Xiaoling; Kuriyakose, Sherine; Van Der Meeren, Olivier; Hardt, Karin; Hezareh, Marjan; Roy-Ghanta, Sumita

    2016-03-14

    Replacing live-attenuated oral poliovirus vaccines (OPV) with inactivated poliovirus vaccines (IPV) is part of the global strategy to eradicate poliomyelitis. China was declared polio-free in 2000 but continues to record cases of vaccine-associated-poliomyelitis and vaccine-derived-poliovirus outbreaks. Two pilot safety studies and two larger immunogenicity trials evaluated the non-inferiority of IPV (Poliorix™, GSK Vaccines, Belgium) versus OPV in infants and booster vaccination in toddlers primed with either IPV or OPV in China. In pilot safety studies, 25 infants received 3-dose IPV primary vaccination (Study A, www.clinicaltrial.gov NCT00937404) and 25 received an IPV booster after priming with three OPV doses (Study B, NCT01021293). In the randomised, controlled immunogenicity and safety trial (Study C, NCT00920439), infants received 3-dose primary vaccination with IPV (N=541) or OPV (N=535) at 2,3,4 months of age, and a booster IPV dose at 18-24 months (N=470, Study D, NCT01323647: extension of study C). Blood samples were collected before and one month post-dose-3 and booster. Reactogenicity was assessed using diary cards. Serious adverse events (SAEs) were captured throughout each study. Study A and B showed that IPV priming and IPV boosting (after OPV) was safe. Study C: One month post-dose-3, all IPV and ≥ 98.3% OPV recipients had seroprotective antibody titres towards each poliovirus type. The immune response elicited by IPV was non-inferior to Chinese OPV. Seroprotective antibody titres persisted in ≥ 94.7% IPV and ≥ 96.1% OPV recipients at 18-24 months (Study D). IPV had a clinically acceptable safety profile in all studies. Grade 3 local and systemic reactions were uncommon. No SAEs were related to IPV administration. Trivalent IPV is non-inferior to OPV in terms of seroprotection (in the Chinese vaccination schedule) in infant and toddlers, with a clinically acceptable safety profile. Copyright © 2016 The Authors. Published by Elsevier Ltd

  6. Cold-Adapted Viral Attenuation (CAVA): Highly Temperature Sensitive Polioviruses as Novel Vaccine Strains for a Next Generation Inactivated Poliovirus Vaccine.

    PubMed

    Sanders, Barbara P; de Los Rios Oakes, Isabel; van Hoek, Vladimir; Bockstal, Viki; Kamphuis, Tobias; Uil, Taco G; Song, Yutong; Cooper, Gillian; Crawt, Laura E; Martín, Javier; Zahn, Roland; Lewis, John; Wimmer, Eckard; Custers, Jerome H H V; Schuitemaker, Hanneke; Cello, Jeronimo; Edo-Matas, Diana

    2016-03-01

    The poliovirus vaccine field is moving towards novel vaccination strategies. Withdrawal of the Oral Poliovirus Vaccine and implementation of the conventional Inactivated Poliovirus Vaccine (cIPV) is imminent. Moreover, replacement of the virulent poliovirus strains currently used for cIPV with attenuated strains is preferred. We generated Cold-Adapted Viral Attenuation (CAVA) poliovirus strains by serial passage at low temperature and subsequent genetic engineering, which contain the capsid sequences of cIPV strains combined with a set of mutations identified during cold-adaptation. These viruses displayed a highly temperature sensitive phenotype with no signs of productive infection at 37°C as visualized by electron microscopy. Furthermore, decreases in infectious titers, viral RNA, and protein levels were measured during infection at 37°C, suggesting a block in the viral replication cycle at RNA replication, protein translation, or earlier. However, at 30°C, they could be propagated to high titers (9.4-9.9 Log10TCID50/ml) on the PER.C6 cell culture platform. We identified 14 mutations in the IRES and non-structural regions, which in combination induced the temperature sensitive phenotype, also when transferred to the genomes of other wild-type and attenuated polioviruses. The temperature sensitivity translated to complete absence of neurovirulence in CD155 transgenic mice. Attenuation was also confirmed after extended in vitro passage at small scale using conditions (MOI, cell density, temperature) anticipated for vaccine production. The inability of CAVA strains to replicate at 37°C makes reversion to a neurovirulent phenotype in vivo highly unlikely, therefore, these strains can be considered safe for the manufacture of IPV. The CAVA strains were immunogenic in the Wistar rat potency model for cIPV, inducing high neutralizing antibody titers in a dose-dependent manner in response to D-antigen doses used for cIPV. In combination with the highly productive

  7. Cold-Adapted Viral Attenuation (CAVA): Highly Temperature Sensitive Polioviruses as Novel Vaccine Strains for a Next Generation Inactivated Poliovirus Vaccine

    PubMed Central

    Sanders, Barbara P.; de los Rios Oakes, Isabel; van Hoek, Vladimir; Bockstal, Viki; Kamphuis, Tobias; Uil, Taco G.; Song, Yutong; Cooper, Gillian; Crawt, Laura E.; Martín, Javier; Zahn, Roland; Lewis, John; Wimmer, Eckard; Custers, Jerome H. H. V.; Schuitemaker, Hanneke; Cello, Jeronimo; Edo-Matas, Diana

    2016-01-01

    The poliovirus vaccine field is moving towards novel vaccination strategies. Withdrawal of the Oral Poliovirus Vaccine and implementation of the conventional Inactivated Poliovirus Vaccine (cIPV) is imminent. Moreover, replacement of the virulent poliovirus strains currently used for cIPV with attenuated strains is preferred. We generated Cold-Adapted Viral Attenuation (CAVA) poliovirus strains by serial passage at low temperature and subsequent genetic engineering, which contain the capsid sequences of cIPV strains combined with a set of mutations identified during cold-adaptation. These viruses displayed a highly temperature sensitive phenotype with no signs of productive infection at 37°C as visualized by electron microscopy. Furthermore, decreases in infectious titers, viral RNA, and protein levels were measured during infection at 37°C, suggesting a block in the viral replication cycle at RNA replication, protein translation, or earlier. However, at 30°C, they could be propagated to high titers (9.4–9.9 Log10TCID50/ml) on the PER.C6 cell culture platform. We identified 14 mutations in the IRES and non-structural regions, which in combination induced the temperature sensitive phenotype, also when transferred to the genomes of other wild-type and attenuated polioviruses. The temperature sensitivity translated to complete absence of neurovirulence in CD155 transgenic mice. Attenuation was also confirmed after extended in vitro passage at small scale using conditions (MOI, cell density, temperature) anticipated for vaccine production. The inability of CAVA strains to replicate at 37°C makes reversion to a neurovirulent phenotype in vivo highly unlikely, therefore, these strains can be considered safe for the manufacture of IPV. The CAVA strains were immunogenic in the Wistar rat potency model for cIPV, inducing high neutralizing antibody titers in a dose-dependent manner in response to D-antigen doses used for cIPV. In combination with the highly productive

  8. Hybrid proteins between Pseudomonas exotoxin A and poliovirus protease 2Apro.

    PubMed

    Novoa, I; Feduchi, E; Carrasco, L

    1994-11-21

    Two hybrid proteins between Pseudomonas aeruginosa exotoxin A (PE) and poliovirus protease 2Apro have been generated. One hybrid protein contains the poliovirus 2Apro sequence replacing the region of PE corresponding to amino acids 413-607. The other hybrid contains in addition the transforming growth factor sequence. The two hybrid proteins were efficiently synthesized in E. coli cells using the inducible pET vectors. Both hybrid toxins cleaved p220 (eIF-4 gamma) when the recombinant plasmids were transfected in COS cells infected with recombinant vaccinia virus bearing the T7 RNA polymerase gene.

  9. Correlation between amount of virus with altered nucleotide sequence and the monkey test for acceptability of oral poliovirus vaccine.

    PubMed Central

    Chumakov, K M; Powers, L B; Noonan, K E; Roninson, I B; Levenbook, I S

    1991-01-01

    Production of live attenuated oral poliomyelitis vaccine (OPV) requires rigorous neurovirulence safety testing of each vaccine lot, currently carried out in monkeys. It has been reported that a change from 472-U to 472-C in the type 3 OPV RNA is associated with an increased histologic lesion score produced upon intraspinal inoculation of the mutant virus in monkeys. We have developed a method, based on polymerase chain reaction, for measuring the relative abundance of these mutant sequences directly in vaccine preparations and used this method to evaluate the proportion of 472-C in 40 different lots of type 3 OPV. Six vaccine lots that had failed the intraspinal monkey neurovirulence test contained a higher proportion of 472-C than all other lots that had passed this test. OPV type 3 virus containing 472-C was rapidly selected during serial passages in African green monkey kidney cells that are used for manufacturing of the vaccine. We have also found that the wild-type poliovirus type 3 strain Leon/37, from which the vaccine strain was originally derived, contained a mixture of 472-U and 472-C sequences. No other mutations in OPV type 3 RNA have been detected by similar assays at position 2034, also associated with attenuation, or at several other positions reported to be altered in some vaccine preparations. Our results suggest that molecular diagnostics may provide a supplement or a potential alternative to animal testing of live attenuated vaccines. Images PMID:1846038

  10. The Poliovirus Empty Capsid Specifically Recognizes the Poliovirus Receptor and Undergoes Some, but Not All, of the Transitions Associated with Cell Entry

    PubMed Central

    Basavappa, Ravi; Gómez-Yafal, Alicia; Hogle, James M.

    1998-01-01

    Experimental results presented here demonstrate that the poliovirus empty capsid binds with saturable character to poliovirus-susceptible cells, binds preferentially to susceptible cells, and competes with mature virus for binding sites on cells. Hence, induced changes in the structure and/or stability of the particle by RNA encapsidation and virus maturation are not necessary for recognition by receptor. In mature virus, heat-induced rearrangements mimic those induced by receptor at physiological temperatures in several important respects, namely, expulsion of VP4 and externalization of the VP1 N-terminal arm. It is shown here that in the empty capsid the VP1 N-terminal arm is externalized but the VP4 portion of VP0 is not. Thus, these two hallmark rearrangements associated with cell entry can be uncoupled. PMID:9696852

  11. Environmental surveillance of poliovirus and non-polio enterovirus in urban sewage in Dakar, Senegal (2007-2013).

    PubMed

    Ndiaye, Abdou Kader; Diop, Pape Amadou Mbathio; Diop, Ousmane Madiagne

    2014-01-01

    Global poliomyelitis eradication initiative relies on (i) laboratory based surveillance of acute flaccid surveillance (AFP) to monitor the circulation of wild poliovirus in a population, and (ii) vaccination to prevent its diffusion. However, as poliovirus can survive in the environment namely in sewage, environmental surveillance (ES) is of growing importance as the eradication target is close. This study aimed to assess polioviruses and non polio enteroviruses circulation in sewage drains covering a significant population of Dakar. From April 2007 to May 2013, 271 specimens of raw sewage were collected using the grab method in 6 neighborhoods of Dakar. Samples were processed to extract and concentrate viruses using polyethylene glycol and Dextran (two-phase separation method). Isolation of enteroviruses was attempted in RD, L20B and Hep2 cell lines. Polioviruses were identified by RT-PCR and Elisa. Non Polio Enteroviruses (NPEVs) were identified by RT-PCR and microneutralisation tests. Polioviruses and NPEVs were respectively detected in 34,3% and 42,8% sewage samples. No wild poliovirus neither circulating vaccine-derived Poliovirus (cVDPV) was detected. Neutralization assays have identified 49 non polio enteroviruses that were subsequently classified in 13 serotypes belonging to HEV-A (22, 4%), HEV-B (12, 24%), HEV-C (26, 53%) and HEV-D (6, 12%) species. This study is the first documentation of enteroviruses environmental detection in Senegal. It shows the usefulness of environmental surveillance for indirect monitoring of the circulation and distribution of enteroviruses in the community.

  12. Characterization of Poliovirus Variants Selected for Resistance to the Antiviral Compound V-073

    PubMed Central

    Liu, Hong-Mei; Roberts, Jason A.; Moore, Deborah; Anderson, Barbara; Pallansch, Mark A.; Pevear, Daniel C.; Collett, Marc S.

    2012-01-01

    V-073, a small-molecule capsid inhibitor originally developed for nonpolio enterovirus indications is considerably more potent against polioviruses. All poliovirus isolates tested to date (n = 45), including wild, vaccine, vaccine-derived, and laboratory strains, are susceptible to the antiviral capsid inhibitor V-073. We grew poliovirus in the presence of V-073 to allow for the identification of variants with reduced susceptibility to the drug. Sequence analysis of 160 independent resistant variants (80 isolates of poliovirus type 1, 40 isolates each of types 2 and 3) established that V-073 resistance involved a single amino acid change in either of two virus capsid proteins, VP1 (67 of 160 [42%]) or VP3 (93 of 160 [58%]). In resistant variants with a VP1 change, the majority (53 of 67 [79%]) exhibited a substitution of isoleucine at position 194 (equivalent position 192 in type 3) with either methionine or phenylalanine. Of those with a VP3 change, alanine at position 24 was replaced with valine in all variants (n = 93). The resistance phenotype was relatively stable upon passage of viruses in cell culture in the absence of drug. Single-step growth studies showed no substantial differences between drug-resistant variants and the virus stocks from which they were derived, while the resistant viruses were generally more thermally labile than the corresponding drug-susceptible parental viruses. These studies provide a foundation from which to build a greater understanding of resistance to antiviral compound V-073. PMID:22890765

  13. Differential depuration of poliovirus, Escherichia coli, and a coliphage by the common mussel, Mytilus edulis

    SciTech Connect

    Power, U.F.; Collins, J.K. )

    1989-06-01

    The elimination of sewage effluent-associated poliovirus, Escherichia coli, and a 22-nm icosahedral coliphage by the common mussel, Mytilus edulis, was studied. Both laboratory-and commercial-scale recirculating, UV depuration systems were used in this study. In the laboratory system, the logarithms of the poliovirus, E. coli, and coliphage levels were reduced by 1.86, 2.9, and 2.16, respectively, within 52 h of depuration. The relative patterns and rates of elimination of the three organisms suggest that they are eliminated from mussels by different mechanisms during depuration under suitable conditions. Poliovirus was not included in experiments undertaken in the commercial-scale depuration system. The differences in the relative rates and patterns of elimination were maintained for E. coli and coliphage in this system, with the logarithm of the E. coli levels being reduced by 3.18 and the logarithm of the coliphage levels being reduced by 0.87. The results from both depuration systems suggest that E. coli is an inappropriate indicator of the efficiency of virus elimination during depuration. The coliphage used appears to be a more representative indicator. Depuration under stressful conditions appeared to have a negligible affect on poliovirus and coliphage elimination rates from mussels. However, the rate and pattern of E. coli elimination were dramatically affected by these conditions. Therefore, monitoring E. coli counts might prove useful in ensuring that mussels are functioning well during depuration.

  14. Purification and properties of poliovirus RNA polymerase expressed in Escherichia coli

    SciTech Connect

    Plotch, S.J.; Palant, O.; Gluzman, Y.

    1989-01-01

    A cDNA clone encoding the RNA polymerase of poliovirus has been expressed in Escherichia coli under the transcriptional control of a T7 bacteriophage promoter. This poliovirus enzyme was designed to contain only a single additional amino acid, the N-terminal methionine. The recombinant enzyme has been purified to near homogeneity, and polyclonal antibodies have been prepared against it. The enzyme exhibits poly(A)-dependent oligo(U)-primed ply(U) polymerase activity as well as RNA polymerase activity. In the presence of an oligo(U) primer, the enzyme catalyzes the synthesis of a full-length copy of either poliovirus or globin RNA templates. In the absence of added primer, RNA products up to twice the length of the template are synthesized. When incubated in the presence of a single nucleoside triphosphate, (..cap alpha..-/sup 32/P)UTP, the enzyme catalyzes the incorporation of radioactive label into template RNA. These results are discussed in light of previously proposed models of poliovirus RNA synthesis in vitro.

  15. Prevention of rhinovirus and poliovirus uncoating by WIN 51711, a new antiviral drug.

    PubMed Central

    Fox, M P; Otto, M J; McKinlay, M A

    1986-01-01

    WIN 51711, a potent new antipicornavirus drug, has been shown to inhibit an early event in the replication cycle of human poliovirus type 2 and human rhinovirus type 2. WIN 51711 was not virucidal and had no measurable effect on the adsorption of [3H]uridine-labeled virions to cells. When virion penetration of the plasma membrane was determined through loss of sensitivity to neutralizing antisera, WIN 51711 had no effect on poliovirus penetration, but inhibited rhinovirus penetration by 40%. In the presence of WIN 51711, exposure of neutral red-encapsidated virus-infected cells to light at 3 h postinfection resulted in a 3-log reduction in the number of infectious centers, indicating that WIN 51711 maintained the viral RNA in the encapsidated state after penetrating the cell membrane. The inhibition of uncoating by WIN 51711 in the neutral red assay was found to be concentration dependent, with a concentration of 0.03 micrograms/ml resulting in a 90% inhibition of uncoating. Sucrose gradient sedimentation of lysates from whole cells infected with [3H]uridine-labeled poliovirus showed that poliovirions remained intact in the presence of WIN 51711, but were uncoated in the absence of drug. WIN 51711 also prevented thermal inactivation of poliovirus infectivity, indicating a direct stabilizing effect of this compound on virion capsid conformation. PMID:3019232

  16. Alternative splicing, a new target to block cellular gene expression by poliovirus 2A protease

    SciTech Connect

    Alvarez, Enrique; Castello, Alfredo; Carrasco, Luis; Izquierdo, Jose M.

    2011-10-14

    Highlights: {yields} Novel role for poliovirus 2A protease as splicing modulator. {yields} Poliovirus 2A protease inhibits the alternative splicing of pre-mRNAs. {yields} Poliovirus 2A protease blocks the second catalytic step of splicing. -- Abstract: Viruses have developed multiple strategies to interfere with the gene expression of host cells at different stages to ensure their own survival. Here we report a new role for poliovirus 2A{sup pro} modulating the alternative splicing of pre-mRNAs. Expression of 2A{sup pro} potently inhibits splicing of reporter genes in HeLa cells. Low amounts of 2A{sup pro} abrogate Fas exon 6 skipping, whereas higher levels of protease fully abolish Fas and FGFR2 splicing. In vitro splicing of MINX mRNA using nuclear extracts is also strongly inhibited by 2A{sup pro}, leading to accumulation of the first exon and the lariat product containing the unspliced second exon. These findings reveal that the mechanism of action of 2A{sup pro} on splicing is to selectively block the second catalytic step.

  17. Vaccine-Derived Polioviruses and Children with Primary Immunodeficiency, Iran, 1995–2014

    PubMed Central

    Shaghaghi, Mohammadreza; Shahmahmoodi, Shohreh; Abolhassani, Hassan; Soleyman-jahi, Saeed; Parvaneh, Leila; Mahmoudi, Sussan; Chavoshzadeh, Zahra; Yazdani, Reza; Zahraei, Seyed Mohsen; Ebrahimi, Mohsen; Eslamian, Mohammad H.; Tabatabaie, Hamideh; Yousefi, Maryam; Kandelousi, Yaghoob M.; Oujaghlou, Aliasghar; Rezaei, Nima

    2016-01-01

    Widespread use of oral poliovirus vaccine has led to an ≈99.9% decrease in global incidence of poliomyelitis (from ≈350,000 cases in 1988 to 74 cases in 2015) and eradication of wild-type poliovirus serotypes 2 and 3. However, patients with primary immunodeficiency might shed vaccine-derived polioviruses (VDPVs) for an extended period, which could pose a major threat to polio eradication programs. Since 1995, sixteen VDPV populations have been isolated from 14 patients with immunodeficiency in Iran. For these patients, vaccine-associated paralysis, mostly in >1 extremity, was the first manifestation of primary immunodeficiency. Seven patients with humoral immunodeficiency cleared VDPV infection more frequently than did 6 patients with combined immunodeficiencies. Our results raise questions about manifestations of VDPVs in immunodeficient patients and the role of cellular immunity against enterovirus infections. On the basis of an association between VDPVs and immunodeficiency, we advocate screening of patients with primary immunodeficiency for shedding of polioviruses. PMID:27648512

  18. Capped mRNAs with reduced secondary structure can function in extracts from poliovirus-infected cells

    SciTech Connect

    Sonenberg, N.; Guertin, D.; Lee, K.A.W.

    1982-12-01

    Extracts form poliovirus-infected HeLa cells were used to study ribosome binding of native and denatured reovirus mRNAs and translation of capped mRNAs with different degrees of secondary structure. Here, the authors demonstrate that ribosomes in extracts from poliovirus-infected cells could form initiation complexes with denatured reovirus mRNA, in contrast to their inability to bind native reovirus mRNA. Furthermore, the capped alfalfa mosiac virus 4 RNA, which is most probable devoid of stable secondary structure at its 5' end, could be translated at much higher efficiency than could other capped mRNAs in extracts from poliovirus-infected cells.

  19. A poliovirus 2A(pro) mutant unable to cleave 3CD shows inefficient viral protein synthesis and transactivation defects.

    PubMed Central

    Ventoso, I; Carrasco, L

    1995-01-01

    Four poliovirus mutants with modifications of tyrosine 88 in 2A(pro) were generated and introduced into the cloned poliovirus genome. Mutants Y88P and Y88L were nonviable, mutant Y88F showed a wild-type (WT) phenotype, and mutant Y88S showed a delayed cytopathic effect and formed small plaques in HeLa cells. Growth of Y88S in HeLa cells was restricted, giving rise to about 20% of the PFU production of the WT poliovirus. The 2A (Y88S) mutant synthesized significantly lower levels of viral proteins in HeLa cells than did the WT poliovirus, while the kinetics of p220 cleavage were identical for both viruses. Strikingly, the 2A (Y88S) mutant was unable to cleave 3CD, as shown by analysis of poliovirus proteins labeled with [35S]methionine or immunoblotted with a specific anti-3C serum. The ability of the Y88S mutant to form infectious virus and cleave 3CD can be complemented by the WT poliovirus. Synthesis of viral RNA was diminished in the Y88S mutant but less than the inhibition of translation of viral RNA. Experiments in which guanidine was used to inhibit poliovirus RNA synthesis suggest that the primary defect of the Y88S mutant virus is at the level of poliovirus RNA translation, while viral genome replication is much less affected. Transfection of HeLa cells infected with the WT poliovirus with a luciferase mRNA containing the poliovirus 5' untranslated sequence gives rise to a severalfold increase in luciferase activity. This enhanced translation of leader-luc mRNA was not observed when the transfected cells were infected with the 2A (Y88S) mutant. Moreover, cotransfection with mRNA encoding WT poliovirus 2A(pro) enhanced translation of leader-luc mRNA. This enhancement was much lower upon transfection with mRNA encoding 2A(Y88S), 2A(Y88L), or 2A(Y88P). These findings support the view that 2A(pro) itself, rather than the 3C' and/or 3D' products, is necessary for efficient translation of poliovirus RNA in HeLa cells. PMID:7666528

  20. Effects of poliovirus 2A(pro) on vaccinia virus gene expression.

    PubMed

    Feduchi, E; Aldabe, R; Novoa, I; Carrasco, L

    1995-12-15

    The effects of transient expression of poliovirus 2A(pro) on p220 cleavage in COS cells have been analyzed. When 2A(pro) was cloned in plasmid pTM1 and transiently expressed in COS cells, efficient cleavage of p220 occurred after infection of these cells with a recombinant vaccinia virus bearing phage T7 RNA polymerase. High numbers of COS cells were transfected with pTM1-2A, as judged by p220 cleavage, thereby allowing an analysis of the effects of poliovirus 2A(pro) on vaccinia virus gene expression. A 40-50% cleavage of p220 by transfected poliovirus 2A(pro) was observed ten hours post infection and cleavage was almost complete (80-90%) 20-25 hours post infection with vaccinia virus. Profound inhibition of vaccinia virus protein synthesis was detectable ten hours post infection and was maximal 20-25 hours post infection. This inhibition resulted from neither a blockade of transcription of vaccinia virus nor a lack of translatability of the mRNAs present in cells that synthesize poliovirus 2A(pro). Addition of ara-C inhibited the replication of vaccinia virus and allowed the continued synthesis of cellular proteins. Under these conditions, 2A(pro) is expressed and blocks cellular translation. Finally, p220 cleavage by 2A(pro) did not inhibit the translation of a mRNA encoding poliovirus protein 2C, as directed by the 5' leader sequences of encephalomiocarditis virus. Therefore, these findings show a correlation between p220 cleavage and inhibition of translation from newly made mRNAs. Our results are discussed in the light of present knowledge of p220 function, and new approaches are considered that might provide further insights into the function(s) of initiation factor eIF-4F.

  1. Five of Five VHHs Neutralizing Poliovirus Bind the Receptor-Binding Site

    PubMed Central

    Strauss, Mike; Schotte, Lise; Thys, Bert; Filman, David J.

    2016-01-01

    ABSTRACT Nanobodies, or VHHs, that recognize poliovirus type 1 have previously been selected and characterized as candidates for antiviral agents or reagents for standardization of vaccine quality control. In this study, we present high-resolution cryo-electron microscopy reconstructions of poliovirus with five neutralizing VHHs. All VHHs bind the capsid in the canyon at sites that extensively overlap the poliovirus receptor-binding site. In contrast, the interaction involves a unique (and surprisingly extensive) surface for each of the five VHHs. Five regions of the capsid were found to participate in binding with all five VHHs. Four of these five regions are known to alter during the expansion of the capsid associated with viral entry. Interestingly, binding of one of the VHHs, PVSS21E, resulted in significant changes of the capsid structure and thus seems to trap the virus in an early stage of expansion. IMPORTANCE We describe the cryo-electron microscopy structures of complexes of five neutralizing VHHs with the Mahoney strain of type 1 poliovirus at resolutions ranging from 3.8 to 6.3Å. All five VHHs bind deep in the virus canyon at similar sites that overlap extensively with the binding site for the receptor (CD155). The binding surfaces on the VHHs are surprisingly extensive, but despite the use of similar binding surfaces on the virus, the binding surface on the VHHs is unique for each VHH. In four of the five complexes, the virus remains essentially unchanged, but for the fifth there are significant changes reminiscent of but smaller in magnitude than the changes associated with cell entry, suggesting that this VHH traps the virus in a previously undescribed early intermediate state. The neutralizing mechanisms of the VHHs and their potential use as quality control agents for the end game of poliovirus eradication are discussed. PMID:26764003

  2. The role of older children and adults in wild poliovirus transmission

    PubMed Central

    Blake, Isobel M.; Martin, Rebecca; Goel, Ajay; Khetsuriani, Nino; Everts, Johannes; Wolff, Christopher; Wassilak, Steven; Aylward, R. Bruce; Grassly, Nicholas C.

    2014-01-01

    As polio eradication inches closer, the absence of poliovirus circulation in most of the world and imperfect vaccination coverage are resulting in immunity gaps and polio outbreaks affecting adults. Furthermore, imperfect, waning intestinal immunity among older children and adults permits reinfection and poliovirus shedding, prompting calls to extend the age range of vaccination campaigns even in the absence of cases in these age groups. The success of such a strategy depends on the contribution to poliovirus transmission by older ages, which has not previously been estimated. We fit a mathematical model of poliovirus transmission to time series data from two large outbreaks that affected adults (Tajikistan 2010, Republic of Congo 2010) using maximum-likelihood estimation based on iterated particle-filtering methods. In Tajikistan, the contribution of unvaccinated older children and adults to transmission was minimal despite a significant number of cases in these age groups [reproduction number, R = 0.46 (95% confidence interval, 0.42–0.52) for >5-y-olds compared to 2.18 (2.06–2.45) for 0- to 5-y-olds]. In contrast, in the Republic of Congo, the contribution of older children and adults was significant [R = 1.85 (1.83–4.00)], perhaps reflecting sanitary and socioeconomic variables favoring efficient virus transmission. In neither setting was there evidence for a significant role of imperfect intestinal immunity in the transmission of poliovirus. Bringing the immunization response to the Tajikistan outbreak forward by 2 wk would have prevented an additional 130 cases (21%), highlighting the importance of early outbreak detection and response. PMID:25002465

  3. Antibody to a synthetic nonapeptide corresponding to the NH2 terminus of poliovirus genome-linked protein VPg reacts with native VPg and inhibits in vitro replication of poliovirus RNA.

    PubMed Central

    Morrow, C D; Dasgupta, A

    1983-01-01

    A synthetic nonapeptide corresponding to the N-terminal sequence of poliovirus genome-linked protein (VPg) was linked to bovine serum albumin and used to raise antibodies in rabbits. The antipeptide antibodies specifically precipitated the nonapeptide, native VPg, and VPg-linked poliovirion RNA. The antipeptide antibodies inhibited host factor-stimulated, poliovirus replicase-catalyzed in vitro synthesis of full-length (35S) RNA in response to virion RNA. Oligouridylic acid-stimulated RNA synthesis was not affected by the antipeptide antibodies. Preincubation of the antibodies with excess nonapeptide reversed the antipeptide antibody-mediated inhibition of host factor-stimulated RNA synthesis by the poliovirus replicase. A role for VPg in the in vitro replication of poliovirus RNA genome is discussed. Images PMID:6312101

  4. Effect of buffer on the immune response to trivalent oral poliovirus vaccine in Bangladesh: a community based randomized controlled trial.

    PubMed

    Chandir, Subhash; Ahamed, Kabir U; Baqui, Abdullah H; Sutter, Roland W; Okayasu, Hiromasa; Pallansch, Mark A; Oberste, Mark S; Moulton, Lawrence H; Halsey, Neal A

    2014-11-01

    Polio eradication efforts have been hampered by low responses to trivalent oral poliovirus vaccine (tOPV) in some developing countries. Since stomach acidity may neutralize vaccine viruses, we assessed whether administration of a buffer solution could improve the immunogenicity of tOPV. Healthy infants 4-6 weeks old in Sylhet, Bangladesh, were randomized to receive tOPV with or without a sodium bicarbonate and sodium citrate buffer at age 6, 10, and 14 weeks. Levels of serum neutralizing antibodies for poliovirus types 1, 2, and 3 were measured before and after vaccination, at 6 and 18 weeks of age, respectively. Serologic response rates following 3 doses of tOPV for buffer recipients and control infants were 95% and 88% (P=.065), respectively, for type 1 poliovirus; 95% and 97% (P=.543), respectively, for type 2 poliovirus; and 90% and 89% (P=.79), respectively, for type 3 poliovirus. Administration of a buffer solution prior to vaccination was not associated with statistically significant increases in the immune response to tOPV; however, a marginal 7% increase (P=.065) in serologic response to poliovirus type 1 was observed. NCT01579825. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  5. Poliovirus-associated protein kinase: Destabilization of the virus capsid and stimulation of the phosphorylation reaction by Zn sup 2+

    SciTech Connect

    Ratka, M.; Lackmann, M.; Ueckermann, C.; Karlins, U.; Koch, G. )

    1989-09-01

    The previously described poliovirus-associated protein kinase activity phosphorylates viral proteins VP0 and VP2 as well as exogenous proteins in the presence of Mg{sup 2+}. In this paper, the effect of Zn{sup 2+} on the phosphorylation reaction and the stability of the poliovirus capsid has been studied in detail and compared to that of Mg{sup 2+}. In the presence of Zn{sup 2+}, phosphorylation of capsid proteins VP2 and VP4 is significantly higher while phosphorylation of VP0 and exogenous phosphate acceptor proteins is not detected. The results indicate the activation of more than one virus-associated protein kinase by Zn{sup 2+}. The ion-dependent behavior of the enzyme activities is observed independently of whether the virus was obtained from HeLa or green monkey kidney cells. The poliovirus capsid is destabilized by Zn{sup 2+}. This alteration of the poliovirus capsid structure is a prerequisite for effective phosphorylation of viral capsid proteins. The increased level of phosphorylation of viral capsid proteins results in further destabilization of the viral capsid. As a result of the conformational changes, poliovirus-associated protein kinase activities dissociate from the virus particle. The authors suggest that the destabilizing effect of phosphorylation on the viral capsid plays a role in uncoating of poliovirus.

  6. Prolonged Excretion of Poliovirus among Individuals with Primary Immunodeficiency Disorder: An Analysis of the World Health Organization Registry.

    PubMed

    Macklin, Grace; Liao, Yi; Takane, Marina; Dooling, Kathleen; Gilmour, Stuart; Mach, Ondrej; Kew, Olen M; Sutter, Roland W

    2017-01-01

    Individuals with primary immunodeficiency disorder may excrete poliovirus for extended periods and will constitute the only remaining reservoir of virus after eradication and withdrawal of oral poliovirus vaccine. Here, we analyzed the epidemiology of prolonged and chronic immunodeficiency-related vaccine-derived poliovirus cases in a registry maintained by the World Health Organization, to identify risk factors and determine the length of excretion. Between 1962 and 2016, there were 101 cases, with 94/101 (93%) prolonged excretors and 7/101 (7%) chronic excretors. We documented an increase in incidence in recent decades, with a shift toward middle-income countries, and a predominance of poliovirus type 2 in 73/101 (72%) cases. The median length of excretion was 1.3 years (95% confidence interval: 1.0, 1.4) and 90% of individuals stopped excreting after 3.7 years. Common variable immunodeficiency syndrome and residence in high-income countries were risk factors for long-term excretion. The changing epidemiology of cases, manifested by the greater incidence in recent decades and a shift to from high- to middle-income countries, highlights the expanding risk of poliovirus transmission after oral poliovirus vaccine cessation. To better quantify and reduce this risk, more sensitive surveillance and effective antiviral therapies are needed.

  7. Viruses in sewage waters during and after a poliomyelitis outbreak and subsequent nationwide oral poliovirus vaccination campaign in Finland.

    PubMed Central

    Pöyry, T; Stenvik, M; Hovi, T

    1988-01-01

    During an outbreak of paralytic poliomyelitis in Finland in 1984 and 1985 the widespread circulation of the causative wild-type serotype 3 poliovirus in the population was documented by demonstrating the virus in sewage water specimens in 13 different locations in the greater Helsinki district and in 13 other cities or towns all over the country. After the nationwide campaign with oral poliovirus vaccine in 1985, poliovirus serotypes 2 and 3 were readily isolated from sewage waters for up to 2 months, whereas type 1 poliovirus seemed to disappear from the sewage more rapidly. All of these isolates were temperature sensitive and therefore most likely vaccine related. The efficacy of the vaccination campaign in regard to elimination of the epidemic type 3 strain was evaluated by a follow-up study on viruses in sewage waters continued for 12 months through the subsequent expected season of poliomyelitis. Several types of enteroviruses, including five vaccine-related poliovirus strains, were identified in the 72 virus-positive specimens out of 93 studied. No wild-type polioviruses were found, indicating the success of the campaign. PMID:2833160

  8. Nectin-like interactions between poliovirus and its receptor trigger conformational changes associated with cell entry.

    PubMed

    Strauss, Mike; Filman, David J; Belnap, David M; Cheng, Naiqian; Noel, Roane T; Hogle, James M

    2015-04-01

    Poliovirus infection is initiated by attachment to a receptor on the cell surface called Pvr or CD155. At physiological temperatures, the receptor catalyzes an irreversible expansion of the virus to form an expanded form of the capsid called the 135S particle. This expansion results in the externalization of the myristoylated capsid protein VP4 and the N-terminal extension of the capsid protein VP1, both of which become inserted into the cell membrane. Structures of the expanded forms of poliovirus and of several related viruses have recently been reported. However, until now, it has been unclear how receptor binding triggers viral expansion at physiological temperature. Here, we report poliovirus in complex with an enzymatically partially deglycosylated form of the 3-domain ectodomain of Pvr at a 4-Å resolution, as determined by cryo-electron microscopy. The interaction of the receptor with the virus in this structure is reminiscent of the interactions of Pvr with its natural ligands. At a low temperature, the receptor induces very few changes in the structure of the virus, with the largest changes occurring within the footprint of the receptor, and in a loop of the internal protein VP4. Changes in the vicinity of the receptor include the displacement of a natural lipid ligand (called "pocket factor"), demonstrating that the loss of this ligand, alone, is not sufficient to induce particle expansion. Finally, analogies with naturally occurring ligand binding in the nectin family suggest which specific structural rearrangements in the virus-receptor complex could help to trigger the irreversible expansion of the capsid. The cell-surface receptor (Pvr) catalyzes a large structural change in the virus that exposes membrane-binding protein chains. We fitted known atomic models of the virus and Pvr into three-dimensional experimental maps of the receptor-virus complex. The molecular interactions we see between poliovirus and its receptor are reminiscent of the nectin

  9. Elevation data collected in 2010 from Sabine National Wildlife Refuge, Louisiana

    USGS Publications Warehouse

    Bernier, Julie C.

    2017-01-01

    This data release serves as an archive of elevation data collected in August 2010 from Sabine National Wildlife Refuge (SNWR), Louisiana. Point (xyz) elevations were collected from historically formed open-water bodies and the surrounding emergent marsh using a combination of stop-and-go (semi-kinematic) and kinematic differential Global Positioning System (DGPS) surveying techniques. These data were collected as part of the U.S. Geological Survey’s (USGS) Gulf Coast Subsidence project and provide more extensive spatial coverage than water depths and marsh-surface elevations collected along coring transects in 2008 (USGS Open-File Report 2011-1169). The elevation data were used to estimate magnitudes of one-dimensional (vertical) and three-dimensional (volume) accommodation that formed as a result of extensive historical wetland loss in the western chenier plain of coastal Louisiana. All elevation data use the projected coordinate system North American Datum of 1983 (NAD83), Universal Transverse Mercator (UTM) Zone 15 North (15N) and all elevations are North American Vertical Datum of 1988 (NAVD88) orthometric heights, derived using the GEOID09 geoid model.

  10. Associations between degraded benthic communities and contaminated sediments: Sabine Lake, Lake Pontchartrain, and Choctawhatchee Bay

    SciTech Connect

    Engle, V.D.; Summers, J.K.; Macauley, J.M.

    1994-12-31

    The Environmental Monitoring and Assessment Program for Estuaries (EMAP-E) in the Gulf of Mexico supplements its base sampling effort each year with localized, intensive spatial sampling in selected large estuarine systems. By selecting random locations within 70 km{sup 2} hexagonal areas, individual estuaries were sampled using EMAP methods but at four times the density as base sampling. In 1992, 19 sites were sampled in Lake Pontchartrain, Louisiana. In 1 993, 18 sites were sampled in Sabine Lake, Texas and 12 sites were sampled in Choctawhatchee Bay, Florida. At all sites, sediment grabs were taken and analyzed for benthic species composition and abundance, for toxicity to Ampelisca, and for organic and inorganic sediment contaminants. An indicator of biotic integrity, the benthic index, was calculated to represent the status of benthic communities. A series of statistical techniques, such as stepwise regression analysis, were employed to determine whether the variation in the benthic index could be associated with variation in sediment contaminants, sediment toxicity, or levels of dissolved oxygen. Spatial distributions of these parameters were examined to determine the geographical co-occurrence of degraded benthic communities and environmental stressors. In Lake Pontchartrain, for example, 85% of the variation in the benthic index was associated with decreased levels of dissolved oxygen, and increased concentrations of PCBs, alkanes, copper, tin, and zinc in the sediments.

  11. Comparative analysis of aroma compounds and sensorial features of strawberry and lemon guavas (Psidium cattleianum Sabine).

    PubMed

    Egea, Mariana Buranelo; Pereira-Netto, Adaucto Bellarmino; Cacho, Juan; Ferreira, Vicente; Lopez, Ricardo

    2014-12-01

    The aroma of strawberry and lemon guava fruits (Psidium cattleianum Sabine) was studied by sensory analysis, gas chromatography-olfactometry (GC-O) and quantitative analysis. Volatiles released from the pulps were collected in a trapping system consisting of LiChrolut EN resins and eluted with dichloromethane/methanol. In total, 23 odour zones were detected by GC-O, of which 16 were found in the extract from the strawberry guava pulp and 17 in the extract from the lemon guava pulp. Among the compounds identified, only 10 were common to both strawberry and lemon guavas. The descriptive sensorial analysis differentiated between the aroma profiles of the strawberry guava pulp with the descriptor "tomato" and the lemon guava pulp with the descriptor "tropical fruit". The typical aroma of the guava fruits was dominated by the presence of numerous aldehydes and ketones among which (Z)-3-hexenal was the most intense odorant, while 1,8-cineole and linalool were also revealed as important aroma constituents.

  12. Virus removal during groundwater recharge: effects of infiltration rate on adsorption of poliovirus to soil

    SciTech Connect

    Vaughn, J.M.; Landry, E.F.; Beckwith, C.A.; Thomas, M.Z.

    1981-01-01

    Studies were conducted to determine the influence of infiltration rate on poliovirus removal during groundwater recharge with tertiary-treated wastewater effluents. Experiments were conducted at a uniquely designed, field-situated test recharge basin facility through which some 62,000 m/sup 3/ of sewage had been previously applied. Recharge at high infiltration rates (75 to 100 cm/h) resulted in the movement of considerable numbers of seeded poliovirus to the groundwater. Moderately reduced infiltration rates (6 cm/h) affected significantly improved virus removal. Very low infiltration rates (0.5 to 1.0 cm/h), achieved by partial clogging of the test basin, yielded the greatest virus removal efficiencies.

  13. Characteristics of districts in Pakistan with persistent transmission of wild poliovirus, 2000-2001.

    PubMed

    Lowther, S A; Mir, T; Bile, M K; Abdul Hafiz, R; Mounts, A W

    2004-01-01

    We sought to identify factors associated with being a reservoir district for wild poliovirus in Pakistan. Differences between reservoir and non-reservoir districts were identified using acute flaccid paralysis surveillance data, population census statistics and data from a survey of district health officials (DHOs). Of the 11 poliovirus reservoir districts identified, population density was significantly higher (median 550 persons/km2) than the non-reservoirs (median 175 persons/km2). DHOs from reservoir districts more often reported that planning was affected by refugees and they had more frequent DHO transfers compared with non-reservoir districts. Multivariate analysis confirmed that reservoirs more often had high population density and frequent DHO transfers. Assessment of district-level and management characteristics can supplement surveillance methods to further improve health programmes.

  14. Simian virus 40, poliovirus vaccines, and human cancer: research progress versus media and public interests

    NASA Technical Reports Server (NTRS)

    Butel, J. S.

    2000-01-01

    From 1955 through early 1963, millions of people were inadvertently exposed to simian virus 40 (SV40) as a contaminant of poliovirus vaccines; the virus had been present in the monkey kidney cultures used to prepare the vaccines and had escaped detection. SV40 was discovered in 1960 and subsequently eliminated from poliovirus vaccines. This article reviews current knowledge about SV40 and considers public responses to reports in the media. SV40 is a potent tumour virus with broad tissue tropism that induces tumours in rodents and transforms cultured cells from many species. It is also an important laboratory model for basic studies of molecular processes in eukaryotic cells and mechanisms of neoplastic transformation. SV40 neutralizing antibodies have been detected in individuals not exposed to contaminated poliovirus vaccines. There have been many reports of detection of SV40 DNA in human tumours, especially mesotheliomas, brain tumours and osteosarcomas; and DNA sequence analyses have ruled out the possibility that the viral DNA in tumours was due to laboratory contamination or that the virus had been misidentified. However, additional studies are necessary to prove that SV40 is the cause of certain human cancers. A recently published review article evaluated the status of the field and received much media attention. The public response emphasized that there is great interest in the possibility of health risks today from vaccinations received in the past.

  15. Effects of poliovirus infection on nucleo-cytoplasmic trafficking and nuclear pore complex composition

    PubMed Central

    Gustin, Kurt E.; Sarnow, Peter

    2001-01-01

    Infection of eukaryotic cells with lytic RNA viruses results in extensive interactions of viral gene products with macromolecular pathways of the host, ultimately leading to death of the infected cells. We show here that infection of cells with poliovirus results in the cytoplasmic accumulation of a variety of shuttling and non-shuttling nuclear proteins that use multiple nuclear import pathways. In vitro nuclear import assays using semi-permeabilized infected cells confirmed that nuclear import was blocked and demonstrated that docking of nuclear import receptor–cargo complexes at the cytoplasmic face of the nuclear pore complex (NPC) was prevented. Analysis of components of the NPC revealed that two proteins, Nup153 and p62, were proteolyzed during poliovirus infection. These results suggest that the cytoplasmic relocalization of numerous cellular proteins is caused by the inhibition of multiple nuclear import pathways via alterations in NPC composition in poliovirus-infected cells. Blocking of nuclear import points to a novel strategy by which cytoplasmic RNA viruses can evade host immune defenses, by preventing signal transduction to the nucleus. PMID:11226174

  16. Massive outbreak of poliomyelitis caused by type-3 wild poliovirus in Angola in 1999.

    PubMed Central

    Valente, F.; Otten, M.; Balbina, F.; Van de Weerdt, R.; Chezzi, C.; Eriki, P.; Van-Dúnnen, J.; Bele, J. M.

    2000-01-01

    The largest outbreak of poliomyelitis ever recorded in Africa (1093 cases) occurred from 1 March to 28 May 1999 in Luanda, Angola, and in surrounding areas. The outbreak was caused primarily by a type-3 wild poliovirus, although type-1 wild poliovirus was circulating in the outbreak area at the same time. Infected individuals ranged in age from 2 months to 22 years; 788 individuals (72%) were younger than 3 years. Of the 590 individuals whose vaccination status was known, 23% had received no vaccine and 54% had received fewer than three doses of oral poliovirus vaccine (OPV). The major factors that contributed to this outbreak were as follows: massive displacement of unvaccinated persons to urban settings; low routine OPV coverage; inaccessible populations during the previous three national immunization days (NIDs); and inadequate sanitation. This outbreak indicates the urgent need to improve accessibility to all children during NIDs and the dramatic impact that war can have by displacing persons and impeding access to routine immunizations. The period immediately after an outbreak provides an enhanced opportunity to eradicate poliomyelitis. If continuous access in all districts for acute flaccid paralysis surveillance and supplemental immunizations cannot be assured, the current war in Angola may threaten global poliomyelitis eradication. PMID:10812730

  17. Cleavage sites in the polypeptide precursors of poliovirus protein P2-X

    SciTech Connect

    Selmer, B.L.; Hanecak, R.; Anderson, C.W.; Wimmer, E.

    1981-01-01

    Partial amino-terminal sequence analysis has been performed on the three major polypeptide products (P2-3b, P2-5b, and P2-X) from the central region (P2) of the poliovirus polyprotein, and this analysis precisely locates the amino termini of these products with respect to the nucleotide sequence of the poliovirus RNA genome. Like most of the products of the replicase region (P3), the amino termini of P2-5b and P2-X are generated by cleavage between glutamine and glycine residues. Thus, P2-5b and P2-X are probably both produced by the action of a singly (virus-encoded.) proteinase. The amino terminus of P2-3b, on the other hand, is produced by a cleavage between the carboxy-terminal tyrosine of VP1 and the glycine encoded by nucleotides 3381-3383. This result may suggest that more than one proteolytic activity is required for the complete processing of the poliovirus polyprotein.

  18. Multiple isoelectric forms of poliovirus RNA-dependent RNA polymerase: Evidence for phosphorylation

    SciTech Connect

    Ransone, L.J.; Dasgupta, A. )

    1989-11-01

    Poliovirus-specific RNA-dependent RNA polymerase (3Dpol) was purified to apparent homogeneity. A single polypeptide of an apparent molecular weight of 63,000 catalyzes the synthesis of dimeric and monomeric RNA products in response to the poliovirion RNA template. Analysis of purified 3Dpol by two-dimensional electrophoresis showed multiple forms of 3Dpol, suggesting posttranslational modification of the protein in virus-infected cells. The two major forms of 3Dpol appear to have approximate pI values of 7.1 and 7.4. Incubation of purified 3Dpol with calf intestinal phosphatase resulted in almost complete disappearance of the pI 7.1 form and a concomitant increase in the intensity of the pI 7.4 form of 3Dpol. Addition of 32P-labeled Pi during infection of HeLa cells with poliovirus resulted in specific labeling of 3Dpol and 3CD, a viral protein which contains the entire 3Dpol sequence. Both 3Dpol and 3CD appear to be phosphorylated at serine residues. Ribosomal salt washes prepared from both mock- and poliovirus-infected cells contain phosphatases capable of dephosphorylating quantitatively the phosphorylated form (pI 7.1) of 3Dpol.

  19. Mechanisms of poliovirus inactivation by the direct and indirect effects of ionizing radiation

    SciTech Connect

    Ward, R.L.

    1980-08-01

    This study was designed to measure the effects of ionizing radiation on poliovirus particles when given under conditions where either direct (in broth) or indirect (in water) effects were predominant. Under direct conditions, inactivation of poliovirus was found to be due primarily to RNA damage, although capsid damage could account for about one-third of the viral inactivation. RNA damage did not appear to be due to strand breakage and therefore was probably caused primarily by base damage or crosslink formation. Capsid damage under direct irradiation conditions did not result in significant alterations of either the sedimentation coefficients or the isoelectric points of the poliovirus particles or detectable modification of the sizes of the viral proteins. It did, however, cause loss of availability to bind to host cells. Under indirect conditions no more than 25% of viral inactivation appeared to be due to RNA damage. However, the sedimentation coefficients and isoelectric points of the viral particles were greatly altered, and their abilities to bind to cells were lost at about three-fourths the rate of loss of infectivity. Capsid damage in this case did result in changes in the sizes of capsid proteins. Therefore, the majority of the radiation inactivation under indirect conditions appeared to be due to protein damage.

  20. Simian virus 40, poliovirus vaccines, and human cancer: research progress versus media and public interests

    NASA Technical Reports Server (NTRS)

    Butel, J. S.

    2000-01-01

    From 1955 through early 1963, millions of people were inadvertently exposed to simian virus 40 (SV40) as a contaminant of poliovirus vaccines; the virus had been present in the monkey kidney cultures used to prepare the vaccines and had escaped detection. SV40 was discovered in 1960 and subsequently eliminated from poliovirus vaccines. This article reviews current knowledge about SV40 and considers public responses to reports in the media. SV40 is a potent tumour virus with broad tissue tropism that induces tumours in rodents and transforms cultured cells from many species. It is also an important laboratory model for basic studies of molecular processes in eukaryotic cells and mechanisms of neoplastic transformation. SV40 neutralizing antibodies have been detected in individuals not exposed to contaminated poliovirus vaccines. There have been many reports of detection of SV40 DNA in human tumours, especially mesotheliomas, brain tumours and osteosarcomas; and DNA sequence analyses have ruled out the possibility that the viral DNA in tumours was due to laboratory contamination or that the virus had been misidentified. However, additional studies are necessary to prove that SV40 is the cause of certain human cancers. A recently published review article evaluated the status of the field and received much media attention. The public response emphasized that there is great interest in the possibility of health risks today from vaccinations received in the past.

  1. Oral iodine supplementation does not reduce neutralizing antibody responses to oral poliovirus vaccine.

    PubMed Central

    Taffs, R. E.; Enterline, J. C.; Rusmil, K.; Muhilal; Suwardi, S. S.; Rustama, D.; Djatnika; Cobra, C.; Semba, R. D.; Cohen, N.; Asher, D. M.

    1999-01-01

    Iodine deficiency is a major cause of impaired mental development, goitre, and cretinism in many parts of the world. Because existing immunization programmes can be used to deliver oral iodized oil (OIO) to infants at risk, it was important to know whether OIO could adversely affect the antibody response to vaccines, such as trivalent oral poliovirus vaccine (OPV). A randomized, double-blind, placebo-controlled clinical trial was conducted in Subang, West Java, Indonesia, in which 617 eight-week-old infants received either OIO or a placebo (poppy-seed oil) during a routine visit for their first dose of OPV as part of the Expanded Programme on Immunization (EPI). The infants received two boosters of OPV at 4-week intervals after the first dose, and were followed up when 6 months old. Neutralizing antibody titres to poliovirus serotypes 1, 2, and 3 were compared in serum samples that were taken from 478 of these infants just before the first dose of OPV and at 6 months. It was found that oral iodized oil did not reduce the antibody responses to any of the three serotypes of OPV. These results indicate that oral iodine may safely be delivered to infants at the same time as oral poliovirus vaccine according to current EPI immunization schedules. PMID:10427933

  2. Mutational analysis of the genome-linked protein VPg of poliovirus.

    PubMed Central

    Kuhn, R J; Tada, H; Ypma-Wong, M F; Semler, B L; Wimmer, E

    1988-01-01

    Using a mutagenesis cartridge (R. J. Kuhn, H. Tada, M. F. Ypma-Wong, J. J. Dunn, B. L. Semler, and E. Wimmer, Proc. Natl. Acad. Sci. USA 85:519-523, 1988), we have generated single and multiple amino acid replacement mutants, as well as a single amino acid insertion mutant in the genome-linked protein VPg of poliovirus. Moreover, we constructed three different 5-amino-acid insertion mutants that map close to the C terminus of 3A, a viral polypeptide whose coding sequence is adjacent to VPg. Transfection of HeLa cells with RNA synthesized in vitro was used to test the effect of the mutation on viral proliferation. Mutations were either lethal or nonlethal. A temperature-sensitive phenotype was not observed. The arginine at position 17 of VPg could not be exchanged with any other amino acid without loss of viability, whereas the lysine at position 20, an amino acid conserved among all known polioviruses, coxsackieviruses, and echoviruses, was replaceable with several neutral amino acids and even with glutamic acid. Replacement of poliovirus VPg with echovirus 9 VPg yielded viable virus with impaired growth properties. Our results suggest considerable flexibility in the amino acid sequence of a functional VPg. All insertions in polypeptide 3A proved to be lethal. In vitro translation of mutated viral RNAs gave patterns of proteolytic processing that in some cases was aberrant, even though the mutation was nonlethal. Images PMID:2845132

  3. Expression of poliovirus 2Apro in mammalian cells: effects on translation.

    PubMed

    Aldabe, R; Feduchi, E; Novoa, I; Carrasco, L

    1995-12-11

    Poliovirus protease 2Apro has been efficiently expressed in HeLa and COS cells upon transfection with vector pTM1-2A and infection with the recombinant vaccinia virus bearing the T7 RNA polymerase. The expressed poliovirus protease localizes to the cytoplasm of the transfected cells, both in the endoplasmic reticulum and in vesicles scattered in the cytoplasm. Cleavage of p220, a component of initiation factor eIF-4F, selectively occurs from 5 h post-infection in transfected cells infected with the recombinant virus. This cleavage correlates in time with the profound inhibition observed in the synthesis of vaccinia virus proteins. A similar blockade of vesicular stomatitis virus translation takes place upon 2Apro expression. Finally, the synthesis of poliovirus protein 2C from a recombinant vaccinia virus that expresses this protein under the EMC untranslated leader region is not affected by the synthesis of 2Apro. These findings lend support to the idea that translation of capped mRNAs requires the integrity of p220, while this requirement is not observed when translation of a mRNA bearing a picornavirus leader region is assayed.

  4. Simian virus 40, poliovirus vaccines, and human cancer: research progress versus media and public interests.

    PubMed Central

    Butel, J. S.

    2000-01-01

    From 1955 through early 1963, millions of people were inadvertently exposed to simian virus 40 (SV40) as a contaminant of poliovirus vaccines; the virus had been present in the monkey kidney cultures used to prepare the vaccines and had escaped detection. SV40 was discovered in 1960 and subsequently eliminated from poliovirus vaccines. This article reviews current knowledge about SV40 and considers public responses to reports in the media. SV40 is a potent tumour virus with broad tissue tropism that induces tumours in rodents and transforms cultured cells from many species. It is also an important laboratory model for basic studies of molecular processes in eukaryotic cells and mechanisms of neoplastic transformation. SV40 neutralizing antibodies have been detected in individuals not exposed to contaminated poliovirus vaccines. There have been many reports of detection of SV40 DNA in human tumours, especially mesotheliomas, brain tumours and osteosarcomas; and DNA sequence analyses have ruled out the possibility that the viral DNA in tumours was due to laboratory contamination or that the virus had been misidentified. However, additional studies are necessary to prove that SV40 is the cause of certain human cancers. A recently published review article evaluated the status of the field and received much media attention. The public response emphasized that there is great interest in the possibility of health risks today from vaccinations received in the past. PMID:10743284

  5. Mapping of the epitopes of poliovirus type 2 in complex with antibodies.

    PubMed

    Bannwarth, Ludovic; Girerd-Chambaz, Yves; Arteni, Ana; Guigner, Jean-Michel; Ronzon, Frederic; Manin, Catherine; Vénien-Bryan, Catherine

    2015-10-01

    The inactivated polio vaccine (IPV) contains poliovirus (PV) samples that belong to serotypes 1, 2 and 3. All three serotypes contain the D-antigen, which induces protective antibodies. The antigenic structure of PVs consists of at least four different antigenic sites and the D-antigen content represents the combined activity of multiple epitopes (Ferguson et al., 1993; Minor, 1990; Minor et al., 1986). The potency of IPV vaccines is determined by measuring the D-antigen content. Several ELISA methods have been developed using polyclonal or monoclonal antibodies (Mabs) in order to quantify the D-antigen content. Characterization of the epitopes recognized by the different Mabs is crucial to map the entire virus surface and ensure the presence of epitopes able to induce neutralizing antibodies. Using a new approach that we developed to study the interaction between monoclonal antibodies and poliovirus type 2, which combines cryo-electron microscopy, image analysis and X-ray crystallography along with identification of exposed amino acids, we have mapped in 3D the epitope sites recognized by three specific Fabs at the surface of poliovirus type 2 (PV2) and characterized precisely the antigenic sites for these Fabs.

  6. National laboratory inventories for wild poliovirus containment--Western Pacific region, 2008.

    PubMed

    2009-09-11

    In the future, when wild poliovirus (WPV) transmission is interrupted worldwide, facilities holding WPV materials will represent the only remaining repository of the virus. Maintaining the number of such facilities at a minimum and at an appropriate biosafety standard (laboratory containment) reduces the risk for a facility-associated reintroduction of WPV. In May 1999, the World Health Assembly (WHA) urged all member states to begin the process leading to laboratory containment of WPV. The World Health Organization (WHO) global action plan for laboratory containment of WPV issued in 1999 indicated a staged approach that begins with a national survey of all biomedical facilities (Phase I); the purpose of the survey is to alert institutions and facilities to the need for containment, encourage reduction of WPV materials, and develop a national inventory of facilities holding such materials. The survey and inventory provide a facility database for use in all subsequent steps toward global poliovirus containment. In May 2008, WHA urged all WHO member states to complete Phase I activities outlined in the WHO Global Action Plan for Laboratory Containment of Wild Polioviruses. In the WHO Western Pacific Region (WPR), Phase I surveys of 77,260 laboratories in the 37 countries and areas of WPR were conducted during 1999--2008. A total of 45 laboratories were identified as holding WPV materials in 2008. This report describes completion of Phase I containment activities by WPR countries, and updates a previous report on Phase I completion in the European Region and global progress.

  7. Poliovirus retention in soil columns after application of chemical- and polyelectrolyte-conditioned dewatered sludges.

    PubMed Central

    Pancorbo, O C; Bitton, G; Farrah, S R; Gifford, G E; Overman, A R

    1988-01-01

    The transport of poliovirus type 1 (strain LSc) was studied in Red Bay sandy loam columns that were treated with chemical- or polyelectrolyte-conditioned dewatered sludges and then leached with natural rainwater under saturated flow conditions. Poliovirus was concentrated in the alum and ferric chloride sludges that were produced following the flocculation of virus-seeded raw sewage. Virtually complete inactivation of the virus was observed following the flocculation of raw sewage or the stabilization of alum and ferric chloride sludges with lime at pH 11.5. Poliovirus was also concentrated in polyelectrolyte-conditioned dewatered sludge that was produced from virus-seeded, anaerobically digested sludge. Despite the saturated flow conditions for a sustained period, no viruses were detected in the leachates of the soil columns that were treated with these chemical and chemically treated sludges. Since the viruses were mostly associated with the solids in these sludge samples, it is believed that they were immobilized along with the sludge solids in the top portion of the soil columns. PMID:2830848

  8. Molecular epidemiology of silent introduction and sustained transmission of wild poliovirus type 1, Israel, 2013.

    PubMed

    Shulman, L M; Gavrilin, E; Jorba, J; Martin, J; Burns, C C; Manor, Y; Moran-Gilad, J; Sofer, D; Hindiyeh, M Y; Gamzu, R; Mendelson, E; Grotto, I

    2014-02-20

    Poliovirus vaccine coverage in Israel is over 90%. The last nine birth cohorts have been vaccinated exclusively with inactivated polio vaccine (IPV). However, between February and July 2013 type 1 wild poliovirus (WPV1) was detected persistently in 10 and intermittently in 8 of 47 environmental surveillance sites in southern and central Israel and in 30 stool samples collected during July from healthy individuals in southern Israel. We report results of sequence and phylogenetic analyses of genes encoding capsid proteins to determine the source and transmission mode of the virus. WPV1 capsid protein 1 nucleotide sequences were most closely related to South Asia (SOAS) cluster R3A polioviruses circulating in Pakistan in 2012 and isolated from Egyptian sewage in December 2012. There was no noticeable geographical clustering within WPV1-positive sites. Uniform codon usage among isolates from Pakistan, Egypt and Israel showed no signs of optimisation or deoptimisation. Bayesian phylogenetic time clock analysis of the entire capsid coding region (2,643 nt) with a 1.1% evolutionary rate indicated that Israeli and Egyptian WPV1-SOAS lineages diverged in September 2012, while Israeli isolates split into two sub-branches after January 2013. This suggests one or more introduction events into Israel with subsequent silent circulation despite high population immunity.

  9. A Stable HeLa Cell Line That Inducibly Expresses Poliovirus 2Apro: Effects on Cellular and Viral Gene Expression

    PubMed Central

    Barco, Angel; Feduchi, Elena; Carrasco, Luis

    2000-01-01

    A HeLa cell clone (2A7d) that inducibly expresses the gene for poliovirus protease 2A (2Apro) under the control of tetracycline has been obtained. Synthesis of 2Apro induces severe morphological changes in 2A7d cells. One day after tetracycline removal, cells round up and a few hours later die. Poliovirus 2Apro cleaves both forms of initiation factor eIF4G, causing extensive inhibition of capped-mRNA translation a few hours after protease induction. Methoxysuccinyl-Ala-Ala-Pro-Val-chloromethylketone, a selective inhibitor of 2Apro, prevents both eIF4G cleavage and inhibition of translation but not cellular death. Expression of 2Apro still allows both the replication of poliovirus and the translation of mRNAs containing a picornavirus leader sequence, while vaccinia virus replication is drastically inhibited. Translation of transfected capped mRNA is blocked in 2A7d-On cells, while luciferase synthesis from a mRNA bearing a picornavirus internal ribosome entry site (IRES) sequence is enhanced by the presence of 2Apro. Moreover, synthesis of 2Apro in 2A7d cells complements the translational defect of a poliovirus 2Apro-defective variant. These results show that poliovirus 2Apro expression mimics some phenotypical characteristics of poliovirus-infected cells, such as cell rounding, inhibition of protein synthesis and enhancement of IRES-driven translation. This cell line constitutes a useful tool to further analyze 2Apro functions, to complement poliovirus 2Apro mutants, and to test antiviral compounds. PMID:10666269

  10. Environmental surveillance of poliovirus and non-polio enterovirus in urban sewage in Dakar, Senegal (2007-2013)

    PubMed Central

    Ndiaye, Abdou Kader; Diop, Pape Amadou Mbathio; Diop, Ousmane Madiagne

    2014-01-01

    Introduction Global poliomyelitis eradication initiative relies on (i) laboratory based surveillance of acute flaccid surveillance (AFP) to monitor the circulation of wild poliovirus in a population, and (ii) vaccination to prevent its diffusion. However, as poliovirus can survive in the environment namely in sewage, environmental surveillance (ES) is of growing importance as the eradication target is close. This study aimed to assess polioviruses and non polio enteroviruses circulation in sewage drains covering a significant population of Dakar. Methods From April 2007 to May 2013, 271 specimens of raw sewage were collected using the grab method in 6 neighborhoods of Dakar. Samples were processed to extract and concentrate viruses using polyethylene glycol and Dextran (two-phase separation method). Isolation of enteroviruses was attempted in RD, L20B and Hep2 cell lines. Polioviruses were identified by RT-PCR and Elisa. Non Polio Enteroviruses (NPEVs) were identified by RT-PCR and microneutralisation tests. Results Polioviruses and NPEVs were respectively detected in 34,3% and 42,8% sewage samples. No wild poliovirus neither circulating vaccine-derived Poliovirus (cVDPV) was detected. Neutralization assays have identified 49 non polio enteroviruses that were subsequently classified in 13 serotypes belonging to HEV-A (22, 4%), HEV-B (12, 24%), HEV-C (26, 53%) and HEV-D (6, 12%) species. Conclusion This study is the first documentation of enteroviruses environmental detection in Senegal. It shows the usefulness of environmental surveillance for indirect monitoring of the circulation and distribution of enteroviruses in the community. PMID:25848458

  11. [Genetic recombination in vaccine poliovirus: comparative study in strains excreted in course of vaccination by oral poliovirus vaccine and circulating strains].

    PubMed

    Haddad-Boubaker, S; Ould-Mohamed-Abdallah, M V; Ben-Yahia, A; Triki, H

    2010-12-01

    Recombination is one of the major mechanisms of evolution in poliovirus. In this work, recombination was assessed in children during vaccination with OPV and among circulating vaccine strains isolated in Tunisia during the last 15 years in order to identify a possible role of recombination in the response to the vaccine or the acquisition of an increased transmissibility. This study included 250 poliovirus isolates: 137 vaccine isolates, excreted by children during primary vaccination with OPV and 113 isolates obtained from acute flaccid paralytic (AFP) cases and healthy contacts. Recombination was first assessed using a double PCR-RFLP, and sequencing. Nineteen per cent of recombinant strains were identified: 20% of strains excreted by vaccinees among 18% of circulating strains. The proportion of recombinant in isolates of serotype1 was very low in the two groups while the proportions of recombinants in serotypes 2 and 3 were different. In vaccinees, the frequency of recombinants in serotype3 decreased during the course of vaccination: 54% after the first dose, 32% after the second and 14% after the third dose. These results suggest that recombination enhances the ability of serotype3 vaccine strains to induce an immune response. Apart from recent vaccination, it may contribute to a more effective transmissibility of vaccine strains among human population. Copyright © 2009 Elsevier Masson SAS. All rights reserved.

  12. Predictive spatial risk model of poliovirus to aid prioritization and hasten eradication in Nigeria

    PubMed Central

    2014-01-01

    Background One of the challenges facing the Global Polio Eradication Initiative is efficiently directing limited resources, such as specially trained personnel, community outreach activities, and satellite vaccinator tracking, to the most at-risk areas to maximize the impact of interventions. A validated predictive model of wild poliovirus circulation would greatly inform prioritization efforts by accurately forecasting areas at greatest risk, thus enabling the greatest effect of program interventions. Methods Using Nigerian acute flaccid paralysis surveillance data from 2004-2013, we developed a spatial hierarchical Poisson hurdle model fitted within a Bayesian framework to study historical polio caseload patterns and forecast future circulation of type 1 and 3 wild poliovirus within districts in Nigeria. A Bayesian temporal smoothing model was applied to address data sparsity underlying estimates of covariates at the district level. Results We find that calculated vaccine-derived population immunity is significantly negatively associated with the probability and number of wild poliovirus case(s) within a district. Recent case information is significantly positively associated with probability of a case, but not the number of cases. We used lagged indicators and coefficients from the fitted models to forecast reported cases in the subsequent six-month periods. Over the past three years, the average predictive ability is 86 ± 2% and 85 ± 4% for wild poliovirus type 1 and 3, respectively. Interestingly, the predictive accuracy of historical transmission patterns alone is equivalent (86 ± 2% and 84 ± 4% for type 1 and 3, respectively). We calculate uncertainty in risk ranking to inform assessments of changes in rank between time periods. Conclusions The model developed in this study successfully predicts districts at risk for future wild poliovirus cases in Nigeria. The highest predicted district risk was 12.8 WPV1 cases in 2006, while the lowest district risk

  13. Attenuation of neurovirulence, biodistribution, and shedding of a poliovirus:rhinovirus chimera after intrathalamic inoculation in Macaca fascicularis.

    PubMed

    Dobrikova, Elena Y; Goetz, Christian; Walters, Robert W; Lawson, Sarah K; Peggins, James O; Muszynski, Karen; Ruppel, Sheryl; Poole, Karyol; Giardina, Steven L; Vela, Eric M; Estep, James E; Gromeier, Matthias

    2012-03-01

    A dependence of poliovirus on an unorthodox translation initiation mode can be targeted selectively to drive viral protein synthesis and cytotoxicity in malignant cells. Transformed cells are naturally susceptible to poliovirus, due to widespread ectopic upregulation of the poliovirus receptor, Necl-5, in ectodermal/neuroectodermal cancers. Viral tumor cell killing and the host immunologic response it engenders produce potent, lasting antineoplastic effects in animal tumor models. Clinical application of this principle depends on unequivocal demonstration of safety in primate models for paralytic poliomyelitis. We conducted extensive dose-range-finding, toxicity, biodistribution, shedding, and neutralizing antibody studies of the prototype oncolytic poliovirus recombinant, PVS-RIPO, after intrathalamic inoculation in Macaca fascicularis. These studies suggest that intracerebral PVS-RIPO inoculation does not lead to viral propagation in the central nervous system (CNS), does not cause histopathological CNS lesions or neurological symptoms that can be attributed to the virus, is not associated with extraneural virus dissemination or replication and does not induce shedding of virus with stool. Intrathalamic PVS-RIPO inoculation induced neutralizing antibody responses against poliovirus serotype 1 in all animals studied.

  14. Cap-independent translation of poliovirus mRNA is conferred by sequence elements within the 5' noncoding region.

    PubMed Central

    Pelletier, J; Kaplan, G; Racaniello, V R; Sonenberg, N

    1988-01-01

    Poliovirus polysomal RNA is naturally uncapped, and as such, its translation must bypass any 5' cap-dependent ribosome recognition event. To elucidate the manner by which poliovirus mRNA is translated, we have determined the translational efficiencies of a series of deletion mutants within the 5' noncoding region of the mRNA. We found striking differences in translatability among the altered mRNAs when assayed in mock-infected and poliovirus-infected HeLa cell extracts. The results identify a functional cis-acting element within the 5' noncoding region of the poliovirus mRNA which enables it to translate in a cap-independent fashion. The major determinant of this element maps between nucleotides 320 and 631 of the 5' end of the poliovirus mRNA. We also show that this region (320 to 631), when fused to a heterologous mRNA, can function in cis to render the mRNA cap independent in translation. Images PMID:2835660

  15. Cap-independent translation of poliovirus mRNA is conferred by sequence elements within the 5' noncoding region

    SciTech Connect

    Pelletier, J.; Kaplan, G.; Racaniello, V.R.; Sonenberg, N.

    1988-03-01

    Poliovirus polysomal RNA is naturally uncapped, and as such, its translation must bypass any 5' cap-dependent ribosome recognition event. To elucidate the manner by which poliovirus mRNA is translated, the authors determined the translational efficiencies of a series of deletion mutants within the 5' noncoding region of the mRNA. They found striking differences in translatability among the altered mRNAs when assayed in mock-infected and poliovirus-infected HeLa cell extracts. The results identify a functional cis-acting element within the 5' noncoding region of the poliovirus mRNA which enables it to translate in a cap-independent fashion. The major determinant of this element maps between nucleotides 320 and 631 of the 5' end of the poliovirus mRNA. They also show that this region (320 to 631), when fused to a heterologous mRNA, can function in cis to render the mRNA cap independent in translation.

  16. Attenuation of Neurovirulence, Biodistribution, and Shedding of a Poliovirus:Rhinovirus Chimera after Intrathalamic Inoculation in Macaca fascicularis

    PubMed Central

    Dobrikova, Elena Y.; Goetz, Christian; Walters, Robert W.; Lawson, Sarah K.; Peggins, James O.; Muszynski, Karen; Ruppel, Sheryl; Poole, Karyol; Giardina, Steven L.; Vela, Eric M.; Estep, James E.

    2012-01-01

    A dependence of poliovirus on an unorthodox translation initiation mode can be targeted selectively to drive viral protein synthesis and cytotoxicity in malignant cells. Transformed cells are naturally susceptible to poliovirus, due to widespread ectopic upregulation of the poliovirus receptor, Necl-5, in ectodermal/neuroectodermal cancers. Viral tumor cell killing and the host immunologic response it engenders produce potent, lasting antineoplastic effects in animal tumor models. Clinical application of this principle depends on unequivocal demonstration of safety in primate models for paralytic poliomyelitis. We conducted extensive dose-range-finding, toxicity, biodistribution, shedding, and neutralizing antibody studies of the prototype oncolytic poliovirus recombinant, PVS-RIPO, after intrathalamic inoculation in Macaca fascicularis. These studies suggest that intracerebral PVS-RIPO inoculation does not lead to viral propagation in the central nervous system (CNS), does not cause histopathological CNS lesions or neurological symptoms that can be attributed to the virus, is not associated with extraneural virus dissemination or replication and does not induce shedding of virus with stool. Intrathalamic PVS-RIPO inoculation induced neutralizing antibody responses against poliovirus serotype 1 in all animals studied. PMID:22171271

  17. Outbreak of paralytic poliomyelitis in Finland: widespread circulation of antigenically altered poliovirus type 3 in a vaccinated population.

    PubMed

    Hovi, T; Cantell, K; Huovilainen, A; Kinnunen, E; Kuronen, T; Lapinleimu, K; Pöyry, T; Roivainen, M; Salama, N; Stenvik, M

    1986-06-21

    An outbreak of 9 cases of paralytic poliomyelitis and 1 non-paralytic case occurred in Finland between August, 1984, and January, 1985, after two decades of freedom from the disease attributable to a successful immunisation programme. During the outbreak poliovirus type 3 was isolated from the patients, from about 15% of healthy persons tested, and from sewage water. At least 100 000 persons were estimated to have been infected. With 1.5 million extra doses of inactivated poliovirus vaccine to children under 18 years of age and an oral poliovirus vaccine campaign covering about 95% of the entire population in February-March, 1985, the outbreak was halted in February, 1985. Impaired herd immunity to the epidemic strain of poliovirus type 3, which differed from the type 3 vaccine strains in both immunological and molecular properties, was important in the emergence of this outbreak. The inactivated poliovaccine that had been used in the vaccination programme was relatively weakly immunogenic, especially as regards the type 3 component. Whether continuous antigenic variation of poliovirus type 3 has wider epidemiological implications is not known.

  18. Poliovirus 5′-Terminal Cloverleaf RNA Is Required in cis for VPg Uridylylation and the Initiation of Negative-Strand RNA Synthesis

    PubMed Central

    Lyons, Traci; Murray, Kenneth E.; Roberts, Allan W.; Barton, David J.

    2001-01-01

    Chimeric poliovirus RNAs, possessing the 5′ nontranslated region (NTR) of hepatitis C virus in place of the 5′ NTR of poliovirus, were used to examine the role of the poliovirus 5′ NTR in viral replication. The chimeric viral RNAs were incubated in cell-free reaction mixtures capable of supporting the sequential translation and replication of poliovirus RNA. Using preinitiation RNA replication complexes formed in these reactions, we demonstrated that the 3′ NTR of poliovirus RNA was insufficient, by itself, to recruit the viral replication proteins required for negative-strand RNA synthesis. The 5′-terminal cloverleaf of poliovirus RNA was required in cis to form functional preinitiation RNA replication complexes capable of uridylylating VPg and initiating the synthesis of negative-strand RNA. These results are consistent with a model in which the 5′-terminal cloverleaf and 3′ NTRs of poliovirus RNA interact via temporally dynamic ribonucleoprotein complexes to coordinately mediate and regulate the sequential translation and replication of poliovirus RNA. PMID:11602711

  19. Monovalent type-1 oral poliovirus vaccine given at short intervals in Pakistan: a randomised controlled, four-arm, open-label, non-inferiority trial

    PubMed Central

    Mir, Fatima; Quadri, Farheen; Mach, Ondrej; Ahmed, Imran; Bhatti, Zaid; Khan, Asia; Rehman, Najeeb ur; Durry, Elias; Salama, Maha; Oberste, Steven M; Weldon, William C; Sutter, Roland W; Zaidi, Anita K M

    2015-01-01

    Summary Background Supplementary immunisation activities with oral poliovirus vaccines (OPVs) are usually separated by 4 week intervals; however, shorter intervals have been used in security-compromised areas and for rapid outbreak responses. We assessed the immunogenicity of monovalent type-1 oral poliovirus vaccine (mOPV1) given at shorter than usual intervals in Karachi, Pakistan. Methods This was a multicentre, randomised, controlled, four-arm, open-label, non-inferiority trial done at five primary health-care centres in low-income communities in and around Karachi, Pakistan. Eligible participants were healthy newborn babies with a birthweight of at least 2.5 kg, for whom informed consent was provided by their parent or guardian, and lived less than 30 km from the study clinic. After receiving a birth dose of trivalent OPV, we enrolled and randomly assigned newborn babies (1:1:1:1) to receive two doses of mOPV1 with an interval of 1 week (mOPV1–1 week), 2 weeks (mOPV1–2 weeks), or 4 weeks (mOPV1–4 weeks) between doses, or two doses of bivalent OPV (bOPV) with an interval of 4 weeks between doses (bOPV–4 weeks). We gave the first study dose of OPV at age 6 weeks. We did the randomisation with a centrally generated, computerised allocation sequence with blocks of 16; participants’ families and study physicians could not feasibly be masked to the allocations. Trial participants were excluded from local supplementary immunisation activities during the study period. The primary outcome was non-inferiority (within a 20% margin) between groups in seroconversion to type-1 poliovirus. The primary and safety analyses were done in the per-protocol population of infants who received all three doses of vaccine. This trial is registered with ClinicalTrials.gov, number NCT01586572, and is closed to new participants. Findings Between March 1, 2012, and May 31, 2013, we enrolled 1009 newborn babies, and randomly assigned 829 (82%) to treatment. 554 (67%) of the 829

  20. Arsenic Removal from Drinking Water by Iron Removal. U.S. EPA Demonstration Project at Sabin, MN. Six-Month Evaluation Report

    EPA Science Inventory

    This report documents the activities performed during and the results obtained from the first six months of the EPA arsenic removal technology demonstration project at the Sabin, MN. The main objective of the project is to evaluate the effectiveness of the Kinetico FM-248-AS ars...

  1. Arsenic Removal from Drinking Water by Iron Removal. U.S. EPA Demonstration Project at Sabin, MN. Six-Month Evaluation Report

    EPA Science Inventory

    This report documents the activities performed during and the results obtained from the first six months of the EPA arsenic removal technology demonstration project at the Sabin, MN. The main objective of the project is to evaluate the effectiveness of the Kinetico FM-248-AS ars...

  2. Arsenic Removal from Drinking Water by Iron Removal U.S. EPA Demonstration Project at Sabin, MN Final Performance Evaluation Report

    EPA Science Inventory

    This report documents the activities performed and the results obtained from January 30, 2006 to April 29, 2007 at the U.S. Environmental Protection Agency (EPA) Arsenic Removal Technology Demonstration site in Sabin, MN. The main objective of the project was to evaluate the eff...

  3. Dynamic profiles of neutralizing antibody responses elicited in rhesus monkeys immunized with a combined tetravalent DTaP-Sabin IPV candidate vaccine.

    PubMed

    Sun, Mingbo; Ma, Yan; Xu, Yinhua; Yang, Huijuan; Shi, Li; Che, Yanchun; Liao, Guoyang; Jiang, Shude; Zhang, Shumin; Li, Qihan

    2014-02-19

    The World Health Organization has recommended that a Sabin inactivated polio vaccine (IPV) should gradually and synchronously replace oral polio vaccines for routine immunizations because its benefits in eliminating vaccine-associated paralytic poliomyelitis have been reported in different phases of clinical trials. It is also considered important to explore new tetravalent diphtheria, tetanus, and acellular pertussis-Sabin IPV (DTaP-sIPV) candidate vaccines for possible use in developing countries. In this study, the immunogenicity of a combined tetravalent DTaP-sIPV candidate vaccine was investigated in primates by evaluating the neutralizing antibody responses it induced. The dynamic profiles of the antibody responses to each of the separate antigenic components and serotypes of Sabin IPV were determined and their corresponding geometric mean titers were similar to those generated by the tetravalent diphtheria, tetanus, and acellular pertussis-conventional IPV (DTaP-cIPV), the tetravalent diphtheria, tetanus, and acellular pertussis (DTaP), and Sabin IPV vaccines in the control groups. This implies that protective immunogenic effects are conferred by this combined tetravalent formulation.

  4. Silent reintroduction of wild-type poliovirus to Israel, 2013 - risk communication challenges in an argumentative atmosphere.

    PubMed

    Kaliner, E; Moran-Gilad, J; Grotto, I; Somekh, E; Kopel, E; Gdalevich, M; Shimron, E; Amikam, Y; Leventhal, A; Lev, B; Gamzu, R

    2014-02-20

    Israel has been certified as polio-free by the World Health Organization and its routine immunisation schedule consists of inactivated poliovirus vaccine (IPV) only. At the end of May 2013, the Israeli Ministry of Health (MOH) has confirmed the reintroduction of wild-type poliovirus 1 into the country. Documented ongoing human-to-human transmission necessitated a thorough risk assessment followed by a supplemental immunisation campaign using oral polio vaccine (OPV). The unusual situation in which ongoing poliovirus transmission was picked up through an early warning system of sewage monitoring without active polio cases, brought about significant challenges in risk communication. This paper reviews the challenges faced by the MOH and the communication strategy devised, in order to facilitate and optimise the various components of the public health response, particularly vaccination. Lessons learned from our recent experience may inform risk communication approaches in other countries that may face a similar situation as global polio eradication moves towards the 'End game'.

  5. Hybrid proteins between Pseudomonas aeruginosa exotoxin A and poliovirus 2Apro cleave p220 in HeLa cells.

    PubMed Central

    Novoa, I; Cotten, M; Carrasco, L

    1996-01-01

    Cleavage of p220, a component of the initiation factor eIF-4F, has been correlated with the inhibition of host translation during poliovirus infection. To obtain p220 cleavage in the absence of any other poliovirus gene products, hybrid proteins containing Pseudomonas aeruginosa exotoxin A and poliovirus protease 2Apro have been constructed. The addition of the hybrid molecules to cultured cells did not lead to substantial p220 cleavage. However, the simultaneous presence of the hybrid toxin with replicationally inactive chicken adenovirus particles results in efficient cleavage of p220 in the intact cells. Under these conditions, cellular translation continues unabated for several hours, arguing against a direct requirement for intact p220 in each round of the initiation of translation of cellular mRNAs. PMID:8627818

  6. Efficient cleavage of p220 by poliovirus 2Apro expression in mammalian cells: effects on vaccinia virus.

    PubMed

    Aldabe, R; Feduchi, E; Novoa, I; Carrasco, L

    1995-10-24

    Poliovirus protease 2A cleaves p220, a component of initiation factor eIF-4F. Polyclonal antibodies that recognize p220 and the cleaved products from different species have been raised. Transfection of several cell lines with poliovirus 2Apro cloned in different plasmids leads to efficient cleavage of p220 upon infection with VT7, a recombinant vaccinia virus that expresses the T7 RNA polymerase. Under these conditions vaccinia virus protein synthesis is severely inhibited, while expression of poliovirus protein 2C from a similar plasmid has no effect. These results show by the first time the effects of p220 cleavage on vaccinia virus translation in the infected cells.

  7. Gene expression in the muscle and central nervous system following intramuscular inoculation of encapsidated or naked poliovirus replicons.

    PubMed

    Jackson, Cheryl A; Messinger, Jeff; Palmer, Matthew T; Peduzzi, Jean D; Morrow, Casey D

    2003-09-15

    The spread of intramuscularly inoculated poliovirus to the central nervous system (CNS) has been documented in humans, monkeys, and mice transgenic for the human poliovirus receptor. Poliovirus spread is thought to be due to infection of the peripheral nerve and retrograde transport of poliovirus through the axon to the neuron cell body, where final virus uncoating occurs and translation/replication ensues. In previous studies, we have shown that polio-based vectors (replicons) can be used for gene delivery to motor neurons of the CNS. Using a replicon that encodes green fluorescent protein (GFP), we found that following intrathecal inoculation, GFP expression was confined to motorneurons of the spinal cord. To further characterize the gene expression of poliovirus in the periphery and CNS, we have intramuscularly inoculated transgenic mice with poliovirus replicons encoding GFP. Expression of GFP was demonstrated in the muscle, sciatic nerve, dorsal root ganglion, and the ventral horn motorneurons following intramuscular inoculation. There was no evidence of paralysis or behavioral abnormalities in the mice following intramuscular inoculation of the replicon encoding GFP. Injection of replicon RNA alone (naked RNA) into the muscle of transgenic mice or rats, which do not express the poliovirus receptor, also resulted in expression of GFP in the muscle, sciatic nerve, dorsal root ganglion, and ventral horn motorneurons, indicating that transport of the replicon RNA from the periphery to CNS had occurred. GFP expression was found in the muscles and sciatic nerve as early as 6 h after injection of replicons or replicon RNA, even after sciatic nerve section. Analysis at longer times postinjection revealed GFP expression similar to 6 h levels in the cut sciatic nerves and robust expression in the nerves of uncut animals. The infection and expression of GFP in the CNS following intramuscular inoculation of encapsidated replicons encoding GFP occurred in juvenile or

  8. A Template RNA Entry Channel in the Fingers Domain of the Poliovirus Polymerase

    PubMed Central

    Kortus, Matthew G.; Kempf, Brian J.; Haworth, Kevin G.; Barton, David J.; Peersen, Olve B.

    2012-01-01

    Positive-strand RNA viruses within the Picornaviridae family express an RNA-dependent RNA polymerase (3Dpol) that is required for viral RNA replication. Structures of 3Dpol from poliovirus, coxsackievirus, human rhinoviruses, and other picornaviruses reveal a putative template RNA entry channel on the surface of the enzyme fingers domain. Basic amino acids and tyrosine residues along this entry channel are predicted to form ionic and base stacking interactions with the viral RNA template as it enters the polymerase active site. We generated a xseries of alanine substitution mutation sat these residues in the poliovirus polymerase and assayed their effects on template RNA binding, RNA synthesis initiation, rates of RNA elongation, elongation complex stability, and virus growth. The results show that basic residues K125, R128, and R188 are important for template RNA binding while tyrosines Y118 and Y148 are required for efficient initiation of RNA synthesis and for elongation complex stability. Alanine substitutions of tyrosines 118 and 148 at the tip of the 3Dpol pinky finger drastically decreased the rate of initiation as well as elongation complex stability, but without affecting template RNA binding or RNA elongation rates. Viable poliovirus was recovered from HeLa cells transfected with mutant RNAs; however, mutations that dramatically inhibited template RNA binding (K125A-K126A and R188A), RNA synthesis initiation (Y118A, Y148A), or elongation complex stability (Y118A, Y148A) were not stably maintained in progeny virus. These data identify key residues within the template RNA entry channel and begin to define their distinct mechanistic roles within RNA elongation complexes. PMID:22321798

  9. Membrane fractions active in poliovirus RNA replication contain VPg precursor polypeptides

    SciTech Connect

    Takegami, T.; Semler, B.L.; Anderson, C.W.; Wimmer, E.

    1983-01-01

    The poliovirus specific polypeptide P3-9 is of special interest for studies of viral RNA replication because it contains a hydrophobic region and, separated by only seven amino acids from that region, the amino acid sequence of the genome-linked protein VPg. Membraneous complexes of poliovirus-infected HeLa cells that contain poliovirus RNA replicating proteins have been analyzed for the presence of P3-9 by immunoprecipitation. Incubation of a membrane fraction rich in P3-9 with proteinase leaves the C-terminal 69 amino acids of P3-9 intact, an observation suggesting that this portion is protected by its association with the cellular membrane. These studies have also revealed two hitherto undescribed viral polypeptides consisting of amino acid sequences of the P2 andf P3 regions of the polyprotein. Sequence analysis by stepwise Edman degradation show that these proteins are 3b/9 (M/sub r/77,000) and X/9 (M/sub r/50,000). 3b/9 and X/9 are membrane bound and are turned over rapidly and may be direct precursors to proteins P2-X and P3-9 of the RNA replication complex. P2-X, a polypeptide void of hydrophobic amino acid sequences but also found associated with membranes, is rapidly degraded when the membraneous complex is treated with trypsin. It is speculated that P2-X is associated with membranes by its affinity to the N-terminus of P3-9.

  10. Mutational analysis of poliovirus 2Apro. Distinct inhibitory functions of 2apro on translation and transcription.

    PubMed

    Ventoso, I; Barco, A; Carrasco, L

    1998-10-23

    Transient expression of poliovirus 2Apro in mammalian cells by means of the recombinant vaccinia virus vT7 expression system leads to drastic inhibition of both cellular and vaccinia virus gene expression (Aldabe, R., Feduchi, E., Novoa, I., and Carrasco, L. (1995) FEBS Lett. 377, 1-5; Aldabe, R., Feduchi, E., Novoa, I., and Carrasco, L. (1995) Biochem. Biophys. Res. Commun. 215, 928-936). To obtain further insights into the molecular basis of this inhibition, a number of 2Apro variants were generated and expressed in COS-1 cells. The effect of these variants on cellular translation, on vaccinia virus-specific translation, and on transcription of the reporter gene luciferase was analyzed. The ability of the different 2Apro variants to block cellular translation depends on their capacities to cleave eIF-4G. The blockade exerted by 2Apro on transcription of the luciferase gene reinforces the notion that this protease is a potent inhibitor of RNA polymerase II-mediated transcription. Some of the 2Apro variants tested failed to block luciferase transcription, despite the fact that eIF-4G cleavage and inhibition of translation were observed. Two reconstituted polioviruses mutated in 2Apro were defective in inhibiting luciferase transcription, yet were still able to cleave eIF-4G and block translation. These findings indicate that 2Apro interferes with cellular gene expression at both the transcriptional and translational levels. Moreover, these two effects probably reflect the inactivation of different host proteins by poliovirus 2Apro.

  11. Poliovirus polypeptide precursors: expression in vitro and processing by exogenous 3C and 2A proteinases.

    PubMed Central

    Nicklin, M J; Kräusslich, H G; Toyoda, H; Dunn, J J; Wimmer, E

    1987-01-01

    Plasmids have been constructed to generate substrates for the study of proteinases 2A and 3C of poliovirus. They contain the P1 (capsomer precursor) region of the poliovirus genome or P1 and part of P2 (a nonstructural precursor), which can be transcribed and translated in vitro. A transcript containing the entire 5' nontranslated region and the P1 region of the viral RNA gave poor translation in a reticulocyte translation system. Truncation of the 5' nontranslated region to its 3'-most segment gave acceptably good yields of radiolabeled P1. P1 was specifically processed to yield capsomer proteins by enzymes supplied in a postmitochondrial supernatant from poliovirus-infected cells. Thus, proteinase 3C can be supplied exogenously (in trans) and effect processing. This system may be used to provide P1 for the assay of proteinase 3C. Precursors that lacked either the 1A or 1D regions were poor substrates for proteinase 3C--observations that demonstrated a stringent structural requirement in processing by 3C. The translation product of a transcript encoding P1 and part of P2 was rapidly cleaved at the P1-P2 site in the absence of infected-cell extract. A transcript that contained a mutated 2A region gave a stable P1-P2 precursor that could be processed specifically by exogenous proteinase from infected-cell fractions. Processing of P1 appeared to require cleavage of the P1-P2 bond. These results support our previous data that 2A is the second polioviral proteinase and also provides a means of assaying proteinase 2A in vitro. Images PMID:3035560

  12. Conditional poliovirus mutants made by random deletion mutagenesis of infectious cDNA.

    PubMed Central

    Kirkegaard, K; Nelsen, B

    1990-01-01

    Small deletions were introduced into DNA plasmids bearing cDNA copies of Mahoney type 1 poliovirus RNA. The procedure used was similar to that of P. Hearing and T. Shenk (J. Mol. Biol. 167:809-822, 1983), with modifications designed to introduce only one lesion randomly into each DNA molecule. Methods to map small deletions in either large DNA or RNA molecules were employed. Two poliovirus mutants, VP1-101 and VP1-102, were selected from mutagenized populations on the basis of their host range phenotype, showing a large reduction in the relative numbers of plaques on CV1 and HeLa cells compared with wild-type virus. The deletions borne by the mutant genomes were mapped to the region encoding the amino terminus of VP1. That these lesions were responsible for the mutant phenotypes was substantiated by reintroduction of the sequenced lesions into a wild-type poliovirus cDNA by deoxyoligonucleotide-directed mutagenesis. The deletion of nucleotides encoding amino acids 8 and 9 of VP1 was responsible for the VP1-101 phenotype; the VP1-102 defect was caused by the deletion of the sequences encoding the first four amino acids of VP1. The peptide sequence at the VP1-VP3 proteolytic cleavage site was altered from glutamine-glycine to glutamine-methionine in VP1-102; this apparently did not alter the proteolytic cleavage pattern. The biochemical defects resulting from these mutations are discussed in the accompanying report. Images PMID:2152811

  13. Modified procedure for the recovery of naturally accumulated poliovirus from oysters.

    PubMed Central

    Vaughn, J M; Landry, E F; Vicale, T J; Dahl, M C

    1979-01-01

    Methods were compared for their ability to recover poliovirus from oysters (Crassostrea gigas) which had been allowed to accumulate virus via normal filtration activities. Clarification procedures included glycine-NaCl and polyelectrolyte extraction methods followed by a variety of acid precipitation concentration methods. Polyelectrolyte flocculation followed by a beef extract-supplemented acid precipitation carried out at pH 3.5 yielded the most efficient recoveries. Direct assay of homogenates was found to be an unreliable method for determining the initial virus concentration in "naturally infected" oysters. PMID:231934

  14. Calcium Flux between the Endoplasmic Reticulum and Mitochondrion Contributes to Poliovirus-Induced Apoptosis▿

    PubMed Central

    Brisac, Cynthia; Téoulé, François; Autret, Arnaud; Pelletier, Isabelle; Colbère-Garapin, Florence; Brenner, Catherine; Lemaire, Christophe; Blondel, Bruno

    2010-01-01

    We show that poliovirus (PV) infection induces an increase in cytosolic calcium (Ca2+) concentration in neuroblastoma IMR5 cells, at least partly through Ca2+ release from the endoplasmic reticulum lumen via the inositol 1,4,5-triphosphate receptor (IP3R) and ryanodine receptor (RyR) channels. This leads to Ca2+ accumulation in mitochondria through the mitochondrial Ca2+ uniporter and the voltage-dependent anion channel (VDAC). This increase in mitochondrial Ca2+ concentration in PV-infected cells leads to mitochondrial dysfunction and apoptosis. PMID:20861253

  15. Live Healthy, Live Longer

    MedlinePlus

    ... Human Services. More Health News on: Exercise and Physical Fitness Health Screening Healthy Living Recent Health News Related MedlinePlus Health Topics Exercise and Physical Fitness Health Screening Healthy Living About MedlinePlus Site Map ...

  16. Search for poliovirus carriers among people with primary immune deficiency diseases in the United States, Mexico, Brazil, and the United Kingdom.

    PubMed Central

    Halsey, Neal A.; Pinto, Jorge; Espinosa-Rosales, Francisco; Faure-Fontenla, María A.; da Silva, Edson; Khan, Aamir J.; Webster, A. D.; Minor, Philip; Dunn, Glynis; Asturias, Edwin; Hussain, Hamidah; Pallansch, Mark A.; Kew, Olen M.; Winkelstein, Jerry; Sutter, Roland

    2004-01-01

    OBJECTIVE: To estimate the rate of long-term poliovirus excretors in people known to have B-cell immune deficiency disorders. METHODS: An active search for chronic excretors was conducted among 306 persons known to have immunoglobulin G (IgG) deficiency in the United States, Mexico, Brazil, and the United Kingdom, and 40 people with IgA deficiency in the United States. Written informed consent or assent was obtained from the participants or their legal guardians, and the studies were formally approved. Stool samples were collected from participants and cultured for polioviruses. Calculation of the confidence interval for the proportion of participants with persistent poliovirus excretion was based on the binomial distribution. FINDINGS: No individuals with long-term excretion of polioviruses were identified. Most participants had received oral poliovirus vaccine (OPV) and almost all had been exposed to household contacts who had received OPV. Polioviruses of recent vaccine origin were transiently found in four individuals in Mexico and Brazil, where OPV is recommended for all children. CONCLUSION: Although chronic poliovirus excretion can occur in immunodeficient persons, it appears to be rare. PMID:15106294

  17. Screening for long-term poliovirus excretion among children with primary immunodeficiency disorders: preparation for the polio posteradication era in Bangladesh.

    PubMed

    Sazzad, Hossain M S; Rainey, Jeanette J; Kahn, Anna-Lea; Mach, Ondrej; Liyanage, Jayantha B L; Alam, Ahmed Nawsher; Kawser, Choudhury A; Hossain, Asgar; Sutter, Roland; Luby, Stephen P

    2014-11-01

    Persons with primary immune deficiency disorders (PIDD) who receive oral poliovirus vaccine (OPV) may transmit immunodeficiency-associated vaccine-derived polioviruses (iVDPVs) and cause paralytic polio. The objective of this study was to identify children with PIDD in Bangladesh, and estimate the proportion with chronic poliovirus excretion. Patients admitted at 5 teaching hospitals were screened for PIDD according to standardized clinical case definitions. PIDD was confirmed by age-specific quantitative immunoglobulin levels. Stool specimens were collected from patients with confirmed PIDD. From February 2011 through January 2013, approximately 96 000 children were screened, and 53 patients were identified who met the clinical case definition for PIDD. Thirteen patients (24%) had age-specific quantitative immunoglobulins results that confirmed PIDD. Of these, 9 (69%) received OPV 3-106 months before stool specimen collection. Among 11 patients, stool specimens from 1 patient tested positive for polioviruses 34 months after OPV ingestion. However, the poliovirus isolate was not available for genetic sequencing, and a subsequent stool specimen 45 days later was negative. The risk of chronic poliovirus excretion among children with PIDD in Bangladesh seems to be low. The national polio eradication program should incorporate strategies for screening for poliovirus excretion among patients with PIDD. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  18. Group-specific identification of polioviruses by PCR using primers containing mixed-base or deoxyinosine residue at positions of codon degeneracy.

    PubMed Central

    Kilpatrick, D R; Nottay, B; Yang, C F; Yang, S J; Mulders, M N; Holloway, B P; Pallansch, M A; Kew, O M

    1996-01-01

    We have developed a method for differentiating polioviruses from nonpolio enteroviruses using PCR. A pair of panpoliovirus PCR primers were designed to match intervals encoding amino acid sequences within VP1 that are strongly conserved among polioviruses. The initiating primer hybridizes with codons of a 7-amino-acid sequence that has been found only in polioviruses; the second primer matches codons of a domain thought to interact with the cell receptor. The panpoliovirus PCR primers contain mixed-base and deoxyinosine residues to compensate for the high degeneracy of the targeted codons. All RNAs from 48 vaccine-related and 110 wild poliovirus isolates of all three serotypes served as efficient templates for amplification of 79-bp product. None of the genomic sequences of 49 nonpolio enterovirus reference strains were amplified under equivalent reaction conditions. Sensitivities of poliovirus detection were as low as 100 fg (equivalent to approximately 25,000 genomic copies or 25 to 250 PFU) when the amplified products were visualized by ethidium bromide fluorescence. These degenerate PCR primers should aid in the detection of all polioviruses, including those wild poliovirus isolates for which genotype-specific reagents are unavailable. PMID:8940436

  19. An outbreak of wild poliovirus in the Republic of Congo, 2010-2011.

    PubMed

    Patel, Minal K; Konde, Mandy Kader; Didi-Ngossaki, Boris Hermann; Ndinga, Edouard; Yogolelo, Riziki; Salla, Mbaye; Shaba, Keith; Everts, Johannes; Armstrong, Gregory L; Daniels, Danni; Burns, Cara; Wassilak, Steve; Pallansch, Mark; Kretsinger, Katrina

    2012-11-15

    The Republic of Congo has had no cases of wild poliovirus type 1 (WPV1) since 2000. In October 2010, a neurologist noted an abnormal number of cases of acute flaccid paralysis (AFP) among adults, which were later confirmed to be caused by WPV1. Those presenting with AFP underwent clinical history, physical examination, and clinical specimen collection to determine if they had polio. AFP cases were classified as laboratory-confirmed, clinical, or nonpolio AFP. Epidemiologic features of the outbreak were analyzed. From 19 September 2010 to 22 January 2011, 445 cases of WPV1 were reported in the Republic of Congo; 390 cases were from Pointe Noire. Overall, 331 cases were among adults; 378 cases were clinically confirmed, and 64 cases were laboratory confirmed. The case-fatality ratio (CFR) was 43%. Epidemiologic characteristics differed among polio cases reported in Pointe Noire and cases reported in the rest of the Republic of Congo, including age distribution and CFR. The outbreak stopped after multiple vaccination rounds with oral poliovirus vaccine, which targeted the entire population. This outbreak underscores the need to maintain high vaccination coverage to prevent outbreaks, the need to maintain timely high-quality surveillance to rapidly identify and respond to any potential cases before an outbreak escalates, and the need to perform ongoing risk assessments of immunity gaps in polio-free countries.

  20. All-atom molecular dynamics calculation study of entire poliovirus empty capsids in solution

    NASA Astrophysics Data System (ADS)

    Andoh, Y.; Yoshii, N.; Yamada, A.; Fujimoto, K.; Kojima, H.; Mizutani, K.; Nakagawa, A.; Nomoto, A.; Okazaki, S.

    2014-10-01

    Small viruses that belong, for example, to the Picornaviridae, such as poliovirus and foot-and-mouth disease virus, consist simply of capsid proteins and a single-stranded RNA (ssRNA) genome. The capsids are quite stable in solution to protect the genome from the environment. Here, based on long-time and large-scale 6.5 × 106 all-atom molecular dynamics calculations for the Mahoney strain of poliovirus, we show microscopic properties of the viral capsids at a molecular level. First, we found equilibrium rapid exchange of water molecules across the capsid. The exchange rate is so high that all water molecules inside the capsid (about 200 000) can leave the capsid and be replaced by water molecules from the outside in about 25 μs. This explains the capsid's tolerance to high pressures and deactivation by exsiccation. In contrast, the capsid did not exchange ions, at least within the present simulation time of 200 ns. This implies that the capsid can function, in principle, as a semipermeable membrane. We also found that, similar to the xylem of trees, the pressure of the solution inside the capsid without the genome was negative. This is caused by coulombic interaction of the solution inside the capsid with the capsid excess charges. The negative pressure may be compensated by positive osmotic pressure by the solution-soluble ssRNA and the counter ions introduced into it.

  1. Poliovirus retention in 75-cm soil cores after sewage and rainwater application

    SciTech Connect

    Landry, E.F.; Vaughn, J.M.; Penello, W.F.

    1980-12-01

    The adsorption rate of a guanidine-resistant strain of poliovirus LSc 2ab was measured in Long Island soils with in situ field cores (10.1 by 75 cm). The test virus was chosen because it exhibited soil adsorption and elution characteristics of a number of non-polioviruses. After the inoculation of cores with seeded sewage effluent at a 1-cm/h infiltration rate, cores were extracted, fractionated, and analyzed for total plaque-forming units per each 5-cm fraction. The results showed that 77% of the viruses were adsorbed in the first 5 cm of soil. An additional 11% were found in the 5- to 10-cm fraction, and a total of 96% of the viruses were adsorbed by 25 cm. The remaining 4% were uniformly distributed over the next 50 cm of soil, with a minimum of 0.23% in each soil section. Few viruses (< 0.22%) were observed in core filtrates. Analysis of the viral distribution pattern in seeded cores, after an application of a single rinse of either sewage effluent or rainwater, indicated that large-scale viral mobilization was absent. However, localized areas of viral movement were noted in both of the rinsed cores, with the rainwater rinsed cores exhibiting more extensive movement. All mobilized viruses were resorbed at lower core depths.

  2. Direct measurement of the poliovirus RNA polymerase error frequency in vitro

    SciTech Connect

    Ward, C.D.; Stokes, M.A.M.; Flanegan, J.B. )

    1988-02-01

    The fidelity of RNA replication by the poliovirus-RNA-dependent RNA polymerase was examined by copying homopolymeric RNA templates in vitro. The poliovirus RNA polymerase was extensively purified and used to copy poly(A), poly(C), or poly(I) templates with equimolar concentrations of noncomplementary and complementary ribonucleotides. The error frequency was expressed as the amount of a noncomplementary nucleotide incorporated divided by the total amount of complementary and noncomplementary nucleotide incorporated. The polymerase error frequencies were very high, depending on the specific reaction conditions. The activity of the polymerase on poly(U) and poly(G) was too low to measure error frequencies on these templates. A fivefold increase in the error frequency was observed when the reaction conditions were changed from 3.0 mM Mg{sup 2+} (pH 7.0) to 7.0 mM Mg{sup 2+} (pH 8.0). This increase in the error frequency correlates with an eightfold increase in the elongation rate that was observed under the same conditions in a previous study.

  3. All-atom molecular dynamics calculation study of entire poliovirus empty capsids in solution

    SciTech Connect

    Andoh, Y.; Yoshii, N.; Yamada, A.; Kojima, H.; Mizutani, K.; Okazaki, S.; Fujimoto, K.; Nakagawa, A.; Nomoto, A.

    2014-10-28

    Small viruses that belong, for example, to the Picornaviridae, such as poliovirus and foot-and-mouth disease virus, consist simply of capsid proteins and a single-stranded RNA (ssRNA) genome. The capsids are quite stable in solution to protect the genome from the environment. Here, based on long-time and large-scale 6.5 × 10{sup 6} all-atom molecular dynamics calculations for the Mahoney strain of poliovirus, we show microscopic properties of the viral capsids at a molecular level. First, we found equilibrium rapid exchange of water molecules across the capsid. The exchange rate is so high that all water molecules inside the capsid (about 200 000) can leave the capsid and be replaced by water molecules from the outside in about 25 μs. This explains the capsid's tolerance to high pressures and deactivation by exsiccation. In contrast, the capsid did not exchange ions, at least within the present simulation time of 200 ns. This implies that the capsid can function, in principle, as a semipermeable membrane. We also found that, similar to the xylem of trees, the pressure of the solution inside the capsid without the genome was negative. This is caused by coulombic interaction of the solution inside the capsid with the capsid excess charges. The negative pressure may be compensated by positive osmotic pressure by the solution-soluble ssRNA and the counter ions introduced into it.

  4. Structural basis for proteolysis-dependent activation of the poliovirus RNA-dependent RNA polymerase

    PubMed Central

    Thompson, Aaron A; Peersen, Olve B

    2004-01-01

    The active RNA-dependent RNA polymerase of poliovirus, 3Dpol, is generated by cleavage of the 3CDpro precursor protein, a protease that has no polymerase activity despite containing the entire polymerase domain. By intentionally disrupting a known and persistent crystal packing interaction, we have crystallized the poliovirus polymerase in a new space group and solved the complete structure of the protein at 2.0 Å resolution. It shows that the N-terminus of fully processed 3Dpol is buried in a surface pocket where it makes hydrogen bonds that act to position Asp238 in the active site. Asp238 is an essential residue that selects for the 2′ OH group of substrate rNTPs, as shown by a 2.35 Å structure of a 3Dpol–GTP complex. Mutational, biochemical, and structural data further demonstrate that 3Dpol activity is exquisitely sensitive to mutations at the N-terminus. This sensitivity is the result of allosteric effects where the structure around the buried N-terminus directly affects the positioning of Asp238 in the active site. PMID:15306852

  5. Development of a novel bag-mediated filtration system for environmental recovery of poliovirus.

    PubMed

    Fagnant, Christine Susan; Beck, Nicola Koren; Yang, Ming-Fong; Barnes, Kilala Sayisha; Boyle, David S; Meschke, John Scott

    2014-12-01

    Poliovirus (PV) is on the verge of global eradication. Due to asymptomatic shedding, eradication certification requires environmental and clinical surveillance. Current environmental surveillance methods involve collection and processing of 400-mL to 1-L grab samples by a two-phase separation method, where sample volume limits detection sensitivity. Filtration of larger sample volumes facilitates increased detection sensitivity. This study describes development of a pumpless in-field filtration system for poliovirus recovery from environmental waters. Recovery of PV types 1, 2, and 3 were compared for glass wool, ViroCap, and NanoCeram (PV1 only) filters. Seeded experiments were performed using 10(5) plaque forming units of PV inoculated into 10-L volumes of secondary effluent, surface water, or a 50:50 mixture of each at pH 7.0. Filter eluates were plated onto buffalo green monkey kidney cells for virus enumeration by plaque assay. Across all water types, recovery from glass wool filters for PV1, PV2, and PV3 averaged 17%, 28%, and 6%, respectively. Recovery from ViroCaps for PV1, PV2, and PV3 averaged 44%, 70%, and 81%, respectively. 10-L samples of moderate turbidity water were processed through ViroCap filters in less than 30 minutes using a pumpless, bag-mediated filtration system. Bag-mediated filtration offers a simple, compact, and efficient method for enhanced environmental PV surveillance.

  6. [Immunoreactivity of chimeric proteins carrying poliovirus epitopes on the VP6 of rotavirus as a vector].

    PubMed

    Pan, X-X; Zhao, B-X; Teng, Y-M; Xia, W-Y; Wang, J; Li, X-F; Liao, G-Y; Yang, С; Chen, Y-D

    2016-01-01

    Rotavirus and poliovirus continue to present significant risks and burden of disease to children in developing countries. Developing a combined vaccine may effectively prevent both illnesses and may be advantageous in terms of maximizing compliance and vaccine coverage at the same visit. Recently, we sought to generate a vaccine vector by incorporating multiple epitopes into the rotavirus group antigenic protein, VP6. In the present study, a foreign epitope presenting a system using VP6 as a vector was created with six sites on the outer surface of the vector that could be used for insertion of foreign epitopes, and three VP6-based PV1 epitope chimeric proteins were constructed. The chimeric proteins were confirmed by immunoblot, immunofluorescence assay, and injected into guinea pigs to analyze the epitope-specific humoral response. Results showed that these chimeric proteins reacted with anti-VP6F and -PV1 antibodies, and elicited antibodies against both proteins in guinea pigs. Antibodies against the chimeric proteins carrying PV1 epitopes neutralized rotavirus Wa and PV1 infection in vitro. Our study contributes to a better understanding of the use of VP6-based vectors as multiple-epitope delivery vehicles and the epitopes displayed in this form could be considered for development of epitope-based vaccines against rotavirus and poliovirus.

  7. Lessons Learned From the Introduction of Inactivated Poliovirus Vaccine in Bangladesh.

    PubMed

    Estivariz, Concepcion F; Snider, Cynthia J; Anand, Abhijeet; Hampton, Lee M; Bari, Tajul I; Billah, Mallick M; Chai, Shua J; Wassilak, Steven G; Heffelfinger, James D; Zaman, K

    2017-07-01

    We assessed programmatic adaptations and infants' uptake of inactivated poliovirus vaccine (IPV) after its introduction into the routine immunization schedule in Bangladesh. Using convenience and probability sampling, we selected 23 health facilities, 36 vaccinators, and 336 caregivers, within 5 districts and 3 city corporations. We collected data during August-October 2015 by conducting interviews, reviewing vaccination records, and observing activities. Knowledge about IPV was high among vaccinators (94%). No problems with IPV storage, transport, or waste disposal were detected, but shortages were reported in 20 health facilities (87%). Wastage per 5-dose vaccine vial was above the recommended 30% in 20 health facilities (87%); all were related to providing <5 doses per open vial. Among eligible infants, 87% and 86% received the third dose of pentavalent and oral poliovirus vaccine, respectively, but only 65% received IPV at the same visit. Among 73 infants not vaccinated with IPV, 58% of caregivers reported that vaccine was unavailable. Bangladesh successfully introduced IPV, but shortages related to insufficient global supply and high vaccine wastage in small outreach immunization sessions might reduce its impact on population immunity. Minimizing wastage and use of a 2-dose fractional-IPV schedule could extend IPV immunization to more children.

  8. Catalysis of poliovirus VP0 maturation cleavage is not mediated by serine 10 of VP2.

    PubMed Central

    Harber, J J; Bradley, J; Anderson, C W; Wimmer, E

    1991-01-01

    The maturation of the poliovirus capsid occurs as the result of a single unexplained proteolytic event during which 58 to 59 copies of the 60 VP0 capsid protein precursors are cleaved. An autocatalytic mechanism for cleavage of VP0 to VP4 and VP2 was proposed by Arnold et al. (E. Arnold, M. Luo, G. Vriend, M. G. Rossman, A. C. Palmenberg, G. D. Parks, M. J. Nicklin, and E. Wimmer, Proc. Natl. Acad. Sci. USA 84:21-25, 1987) in which serine 10 of VP2 is activated by virion RNA to catalyze VP4-VP2 processing. The hypothesis rests on the observation that a hydrogen bond was observed between serine 10 of VP2 (S2010) and the carboxyl terminus of VP4 in three mature picornaviral atomic structures: rhinovirus 14, mengovirus, and poliovirus type 1 (Mahoney). We constructed mutant viruses with cysteine (S2010C) or alanine (S2010A) replacing serine 10 of VP2; these exhibited normal proteolytic processing of VP0. While our results do not exclude an autocatalytic mechanism for the maturation cleavage, they do eliminate the conserved S2010 residue as the catalytic amino acid. Images PMID:1845893

  9. Translational efficiency of poliovirus mRNA: mapping inhibitory cis-acting elements within the 5' noncoding region.

    PubMed Central

    Pelletier, J; Kaplan, G; Racaniello, V R; Sonenberg, N

    1988-01-01

    Poliovirus mRNA contains a long 5' noncoding region of about 750 nucleotides (the exact number varies among the three virus serotypes), which contains several AUG codons upstream of the major initiator AUG. Unlike most eucaryotic mRNAs, poliovirus does not contain a m7GpppX (where X is any nucleotide) cap structure at its 5' end and is translated by a cap-independent mechanism. To study the manner by which poliovirus mRNA is expressed, we examined the translational efficiencies of a series of deletion mutants within the 5' noncoding region of the mRNA. In this paper we report striking translation system-specific differences in the ability of the altered mRNAs to be translated. The results suggest the existence of an inhibitory cis-acting element(s) within the 5' noncoding region of poliovirus (between nucleotides 70 and 381) which restricts mRNA translation in reticulocyte lysate, wheat germ extract, and Xenopus oocytes, but not in HeLa cell extracts. In addition, we show that HeLa cell extracts contain a trans-acting factor(s) that overcomes this restriction. Images PMID:2836606

  10. Viral precursor protein P3 and its processed products perform discrete and essential functions in the poliovirus RNA replication complex

    USDA-ARS?s Scientific Manuscript database

    The differential use of protein precursors and their products is a key strategy used during poliovirus replication. To characterize the role of protein precursors during replication, we examined the complementation profiles of mutants that inhibited 3D polymerase or 3C-RNA binding activity. We showe...

  11. Initiation of poliovirus plus-strand RNA synthesis in a membrane complex of infected HeLa cells

    SciTech Connect

    Takeda, N.; Kuhn, R.J.; Yang, C.F.; Takegami, T.; Wimmer, E.

    1986-10-01

    An in vitro poliovirus RNA-synthesizing system derived from a crude membrance fraction of infected HeLa cells was used to analyze the mechanism of initiation of poliovirus plus-strand RNA synthesis. This system contains an activity that synthesizes the nucleotidyl proteins VPg-pU and VPg-pUpU. These molecules represent the 5'-terminal structure of nascent RNA molecules and of virion RNA. The membranous replication complex is also capable of synthesizing mucleotidyl proteins containing nine or more of the poliovirus 5'-proximal nucleotides as assayed by the formation of the RNase T/sub 1/-resistant oligonucleotide VPg-pUUAAAACAGp or by fingerprint analysis of the in vitro-synthesized /sup 32/P-RNA. Incubation of preformed VPg-pUpU with unlabeled nucleoside triphosphates resulted in the formation of VPg-pUUAAAACAGp. This reaction, which appeared to be an elongation of VPg-pUpU, was stimulated by the addition of a soluble fraction (S-10) obtained from uninfected HeLa cells. Preformed VPg-pU could be chased into VPg-pUpU in the presence of UTP. The data are consistent with a model that VPg-pU can function as a primer for poliovirus plus-strand RNA synthesis in the membranous replication complex and that the elongation reaction may be stimulated by a host cellular factor.

  12. Radiometric cytolysis inhibition assay, a new rapid test for neutralizing antibodies to intact and trypsin-cleaved poliovirus

    SciTech Connect

    Hovi, T.; Roivainen, M.

    1989-04-01

    We have developed a new rapid test, the radiometric cytolysis inhibition assay (RACINA), for the determination of neutralizing poliovirus antibodies. HeLa cells prelabeled with /sup 51/Cr, (/sup 3/H)leucine, or, preferentially, with (/sup 3/H)uridine are used as sensitive quantitative indicators of residual infectious virus. Both suspensions and monolayer cultures of the indicator cells can be used. Neutralization of a fraction of a high-titer virus preparation can be scored after the first replication cycle at 8 to 10 h. By lowering the incubation temperature to 30/degree/C, the completion of the cytolysis due to the first replication cycle of poliovirus was delayed beyond 21 h. This makes it possible to use the RACINA, unlike the standard microneutralization assay, for measuring antibodies to trypsin-cleaved polioviruses. The RACINA was found to be as sensitive as and more reproducible than the standard microneutralization assay in the measurement of neutralizing poliovirus antibodies. The RACINA is a rapid and reliable test for neutralizing antibodies and in principle it may be applicable for quantitation of neutralizing antibodies to other cytolytic agents as well.

  13. The Role of Electron Microscopy in Studying the Continuum of Changes in Membranous Structures during Poliovirus Infection.

    PubMed

    Rossignol, Evan D; Yang, Jie E; Bullitt, Esther

    2015-10-12

    Replication of the poliovirus genome is localized to cytoplasmic replication factories that are fashioned out of a mixture of viral proteins, scavenged cellular components, and new components that are synthesized within the cell due to viral manipulation/up-regulation of protein and phospholipid synthesis. These membranous replication factories are quite complex, and include markers from multiple cytoplasmic cellular organelles. This review focuses on the role of electron microscopy in advancing our understanding of poliovirus RNA replication factories. Structural data from the literature provide the basis for interpreting a wide range of biochemical studies that have been published on virus-induced lipid biosynthesis. In combination, structural and biochemical experiments elucidate the dramatic membrane remodeling that is a hallmark of poliovirus infection. Temporal and spatial membrane modifications throughout the infection cycle are discussed. Early electron microscopy studies of morphological changes following viral infection are re-considered in light of more recent data on viral manipulation of lipid and protein biosynthesis. These data suggest the existence of distinct subcellular vesicle populations, each of which serves specialized roles in poliovirus replication processes.

  14. Isolation and characterization of a type 2 vaccine-derived poliovirus from environmental surveillance in China, 2012.

    PubMed

    Tao, Zexin; Zhang, Yong; Liu, Yao; Xu, Aiqiang; Lin, Xiaojuan; Yoshida, Hiromu; Xiong, Ping; Zhu, Shuangli; Wang, Suting; Yan, Dongmei; Song, Lizhi; Wang, Haiyan; Cui, Ning; Xu, Wenbo

    2013-01-01

    Environmental surveillance of poliovirus on sewage has been conducted in Shandong Province, China since 2008. A type 2 vaccine-derived poliovirus (VDPV) with 7 mutations in VP1 coding region was isolated from the sewage collected in the city of Jinan in December 2012. The complete genome sequencing analysis of this isolate revealed 25 nucleotide substitutions, 7 of which resulted in amino acid alteration. No evidence of recombination with other poliovirus serotypes was observed. The virus did not lose temperature sensitive phenotype at 40°C. An estimation based on the evolution rate of the P1 coding region suggested that evolution time of this strain might be 160-176 days. VP1 sequence analysis revealed that this VDPV strain is of no close relationship with other local type 2 polioviruses (n=66) from sewage collected between May 2012 and June 2013, suggesting the lack of its circulation in the local population. The person who excreted the virus was not known and no closely related virus was isolated in local population via acute flaccid paralysis surveillance. By far this is the first report of VDPV isolated from sewage in China, and these results underscore the value of environmental surveillance in the polio surveillance system even in countries with high rates of OPV coverage.

  15. A coral-based reconstruction of sea surface salinity at Sabine Bank, Vanuatu from 1842 to 2007 CE

    NASA Astrophysics Data System (ADS)

    Gorman, Meaghan K.; Quinn, Terrence M.; Taylor, Frederick W.; Partin, Judson W.; Cabioch, Guy; Austin, James A., Jr.; Pelletier, Bernard; Ballu, Valérie; Maes, Christophe; Saustrup, Steffen

    2012-09-01

    Climate variability associated with the El Niño Southern Oscillation (ENSO) results in large sea-surface temperature (SST) and sea-surface salinity (SSS) anomalies in many regions of the tropical Pacific Ocean. We investigate interannual changes in SSS driven by ENSO in the southwestern Pacific at Sabine Bank, Vanuatu (SBV, 166.04°E, 15.94°S) using monthly variations in coralδ18O from 1842 to 2007 CE. We develop and apply a coral δ18O-SSS transfer function, which is assessed using a calibration-verification exercise (1970-2007 CE). The 165-year reconstructed SSS record contains a prominent trend toward freshening from 1842 to 2007 CE; mean SSS for 1842-1872 CE is 35.46 ± 0.28 psu, which contrasts with a mean value of 34.85 ± 0.31 psu for 1977-2007 CE, with a freshening trend during the latter part of the 20th century that is not unprecedented with respect to the overall record. Variance in the record is concentrated in the interannual (42%) and interdecadal (29%) bands. The SBV-SSS record matches well with a similarly reconstructed SSS time series at Malo Channel, Vanuatu, which is located ˜120 km to the east of SBV. This regional signal is likely driven by ENSO-related changes in the SPCZ and interdecadal changes in surface water advection. The pattern of interdecadal variability at SBV agrees reasonably well with coral records of interdecadal variability from Fiji and Tonga, especially in the pre-1940 portions of the records, further evidence for the regional extent of the salinity signal at Sabine Bank, Vanuatu.

  16. An overview of historical channel adjustment and selected hydraulic values in the Lower Sabine and Lower Brazos River Basins, Texas and Louisiana

    USGS Publications Warehouse

    Heitmuller, Franklin T.; Greene, Lauren E.; John D. Gordon, John D.

    2010-01-01

    The Sabine and Brazos are alluvial rivers; alluvial rivers are dynamic systems that adjust their geometry in response to changes in streamflow (discharge) and sediment load. In fluvial geomorphology, the term 'channel adjustment' refers to river channel changes in three geometric dimensions: (1) channel slope (profile); (2) the outline or shape, such as meandering or braided, projected on a horizontal plane (planform); and (3) cross-sectional form (shape). The primary objective of the study was to investigate how the channel morphology of these rivers has changed in response to reservoirs and other anthropogenic disturbances that have altered streamflow and sediment load. The results of this study are expected to aid ecological assessments in the lower Sabine River and lower Brazos River Basins for the Texas Instream Flow Program. Starting in the 1920s, several dams have been constructed on the Sabine and Brazos Rivers and their tributaries, and numerous bridges have been built and sometimes replaced multiple times, which have changed the natural flow regime and reduced or altered sediment loads downstream. Changes in channel geometry over time can reduce channel conveyance and thus streamflow, which can have adverse ecological effects. Channel attributes including cross-section form, channel slope, and planform change were evaluated to learn how each river's morphology changed over many years in response to natural and anthropogenic disturbances. Climate has large influence on the hydrologic regimes of the lower Sabine and lower Brazos River Basins. Equally important as climate in controlling the hydrologic regime of the two river systems are numerous reservoirs that regulate downstream flow releases. The hydrologic regimes of the two rivers and their tributaries reflect the combined influences of climate, flow regulation, and drainage area. Historical and contemporary cross-sectional channel geometries at 15 streamflow-gaging stations in the lower Sabine and

  17. Poliovirus infection induces the co-localization of cellular protein SRp20 with TIA-1, a cytoplasmic stress granule protein

    PubMed Central

    Fitzgerald, Kerry D.; Semler, Bert L.

    2013-01-01

    Different types of environmental stress cause mammalian cells to form cytoplasmic foci, termed stress granules, which contain mRNPs that are translationally silenced. These foci are transient and dynamic, and contain components of the cellular translation machinery as well as certain mRNAs and RNA binding proteins. Stress granules are known to be induced by conditions such as hypoxia, nutrient deprivation, and oxidative stress, and a number of cellular factors have been identified that are commonly associated with these foci. More recently it was discovered that poliovirus infection also induces the formation of stress granules, although these cytoplasmic foci appear to be somewhat compositionally unique. Work described here examined the punctate pattern of SRp20 (a host cell mRNA splicing protein) localization in the cytoplasm of poliovirus-infected cells, demonstrating the partial co-localization of SRp20 with the stress granule marker protein TIA-1. We determined that SRp20 does not co-localize with TIA-1, however, under conditions of oxidative stress, indicating that the close association of these two proteins during poliovirus infection is not representative of a general response to cellular stress. We confirmed that the expression of a dominant negative version of TIA-1 (TIA-1-PRD) results in the dissociation of stress granules. Finally, we demonstrated that expression of wild type TIA-1 or dominant negative TIA-1-PRD in cells during poliovirus infection does not dramatically affect viral translation. Taken together, these studies provide a new example of the unique cytoplasmic foci that form during poliovirus infection. PMID:23830997

  18. Poliovirus infection induces the co-localization of cellular protein SRp20 with TIA-1, a cytoplasmic stress granule protein.

    PubMed

    Fitzgerald, Kerry D; Semler, Bert L

    2013-09-01

    Different types of environmental stress cause mammalian cells to form cytoplasmic foci, termed stress granules, which contain mRNPs that are translationally silenced. These foci are transient and dynamic, and contain components of the cellular translation machinery as well as certain mRNAs and RNA binding proteins. Stress granules are known to be induced by conditions such as hypoxia, nutrient deprivation, and oxidative stress, and a number of cellular factors have been identified that are commonly associated with these foci. More recently it was discovered that poliovirus infection also induces the formation of stress granules, although these cytoplasmic foci appear to be somewhat compositionally unique. Work described here examined the punctate pattern of SRp20 (a host cell mRNA splicing protein) localization in the cytoplasm of poliovirus-infected cells, demonstrating the partial co-localization of SRp20 with the stress granule marker protein TIA-1. We determined that SRp20 does not co-localize with TIA-1, however, under conditions of oxidative stress, indicating that the close association of these two proteins during poliovirus infection is not representative of a general response to cellular stress. We confirmed that the expression of a dominant negative version of TIA-1 (TIA-1-PRD) results in the dissociation of stress granules. Finally, we demonstrated that expression of wild type TIA-1 or dominant negative TIA-1-PRD in cells during poliovirus infection does not dramatically affect viral translation. Taken together, these studies provide a new example of the unique cytoplasmic foci that form during poliovirus infection. Copyright © 2013 Elsevier B.V. All rights reserved.

  19. Replication of poliovirus RNA and subgenomic RNA transcripts in transfected cells.

    PubMed Central

    Collis, P S; O'Donnell, B J; Barton, D J; Rogers, J A; Flanegan, J B

    1992-01-01

    Full-length and subgenomic poliovirus RNAs were transcribed in vitro and transfected into HeLa cells to study viral RNA replication in vivo. RNAs with deletion mutations were analyzed for the ability to replicate in either the absence or the presence of helper RNA by using a cotransfection procedure and Northern (RNA) blot analysis. An advantage of this approach was that viral RNA replication and genetic complementation could be characterized without first isolating conditional-lethal mutants. A subgenomic RNA with a large in-frame deletion in the capsid coding region (P1) replicated more efficiently than full-length viral RNA transcripts. In cotransfection experiments, both the full-length and subgenomic RNAs replicated at slightly reduced levels and appeared to interfere with each other's replication. In contrast, a subgenomic RNA with a similarly sized out-of-frame deletion in P1 did not replicate in transfected cells, either alone or in the presence of helper RNA. Similar results were observed with an RNA transcript containing a large in-frame deletion spanning the P1, P2, and P3 coding regions. A mutant RNA with an in-frame deletion in the P1-2A coding sequence was self-replicating but at a significantly reduced level. The replication of this RNA was fully complemented after cotransfection with a helper RNA that provided 2A in trans. A P1-2A-2B in-frame deletion, however, totally blocked RNA replication and was not complemented. Control experiments showed that all of the expected viral proteins were both synthesized and processed when the RNA transcripts were translated in vitro. Thus, our results indicated that 2A was a trans-acting protein and that 2B and perhaps other viral proteins were cis acting during poliovirus RNA replication in vivo. Our data support a model for poliovirus RNA replication which directly links the translation of a molecule of plus-strand RNA with the formation of a replication complex for minus-strand RNA synthesis. Images PMID

  20. Establishment of a poliovirus oral infection system in human poliovirus receptor-expressing transgenic mice that are deficient in alpha/beta interferon receptor.

    PubMed

    Ohka, Seii; Igarashi, Hiroko; Nagata, Noriyo; Sakai, Mai; Koike, Satoshi; Nochi, Tomonori; Kiyono, Hiroshi; Nomoto, Akio

    2007-08-01

    Poliovirus (PV) is easily transferred to humans orally; however, no rodent model for oral infections has been developed because of the alimentary tract's low sensitivity to the virus. Here we showed that PV is inactivated by the low pH of the gastric contents in mice. The addition of 3% NaHCO3 to the viral inoculum increased the titer of virus reaching the small intestine through the stomach after intragastric inoculation of PV. Transgenic mice (Tg) carrying the human PV receptor (hPVR/CD155) gene and lacking the alpha/beta interferon receptor (IFNAR) gene (hPVR-Tg/IfnarKO) were sensitive to the oral administration of PV with 3% NaHCO3, whereas hPVR-Tg expressing IFNAR were much less sensitive. The virus was detected in the epithelia of the small intestine and proliferated in the alimentary tract of hPVR-Tg/IfnarKO. By the ninth day after the administration of a virulent PV, the mice had died. These results suggest that IFNAR plays an important role in determining permissivity in the alimentary tract as well as the generation of virus-specific immune responses to PV via the oral route. Thus, hPVR-Tg/IfnarKO are considered to be the first oral infection model for PV, although levels of anti-PV antibodies were not elevated dramatically in serum and intestinal secretions of surviving mice when hPVR-Tg/IfnarKO were administered an attenuated PV.

  1. Seroprevalence of poliovirus antibodies among 7-month-old infants after 4 doses of oral polio vaccine in Sistan-va-Baluchestan, Islamic Republic of Iran.

    PubMed

    Izadi, S; Shahmahmoodi, S; Zahraei, S M; Dorostkar, F; Majdzadeh, S-R

    2015-04-02

    Despite high coverage rates of polio vaccine in the Islamic Republic of Iran, the seroconversion rates of infants may be inadequate. This study measured seroprevalence of antibodies against poliovirus serotypes 1 to 3 (PV1, PV2 and PV3) in 7-month-old infants who had received at least 4 doses of trivalent oral polio vaccine. A serosurvey was conducted in 2010 in rural areas of Chabahar, Sistan-va-Baluchestan province. Using cluster sampling, 72 eligible infants were tested for antibody against the 3 poliovirus serotypes according to WHO guidelines. Antibody titres ≥ 1:10 were considered positive. The seropositive rates for antibody against PV1, PV2 and PV3 were 84.7%, 95.8% and 70.8% respectively. Only 63.9% of participants were seropositive for antibodies against all 3 poliovirus serotypes. Except for PV2, the seroprevalence of antibody against the other 2 poliovirus serotypes, especially PV3, was unsatisfactory.

  2. Elevations and discharges produced by a simulated flood wave on the lower Sabine River, Louisiana and Texas, caused by a theoretical dam failure

    USGS Publications Warehouse

    Neely, Braxtel L.; Stiltner, Gloria J.

    1979-01-01

    The Toledo Bend Reservoir is located on the lower Sabine River between Louisiana and Texas. Two mathematical models were coupled to calculate the flood wave that would result from the theoretical failure of 25 percent of Toledo Bend Dam and route the wave downstream to Orange, Tex. Computations assumed failure (1) at the peak of the 100-year flood when discharge of the Sabine River is 102,000 cubic feet per second and (2) when the average discharge is 10,000 cubic feet per second. Two techniques were used in the dam-break model. The method of characteristics was used to propagate the shock wave following dam failure. The linear implicit finite-difference solution was used to route the flood wave following shock wave dissipation. The magnitude of the flow was determined for Burkeville, Bon Wier, Ruliff, and Orange, Tex., along the lower Sabine River. For these sites, respectively, the following peak elevations were calculated: 119, 82, 31, and 13 feet for the 100-year flood and 110, 75, 27, and 9 feet for the average discharge. (Woodard-USGS)

  3. Molecular Characterization and Phylogenetic Relationship of Wild Type 1 Poliovirus Strains Circulating across Pakistan and Afghanistan Bordering Areas during 2010–2012

    PubMed Central

    Shaukat, Shahzad; Angez, Mehar; Alam, Muhammad Masroor; Sharif, Salmaan; Khurshid, Adnan; Malik, Farzana; Rehman, Lubna; Zaidi, Syed Sohail Zahoor

    2014-01-01

    Pakistan and Afghanistan share a long uncontrolled border with extensive population movement on both sides. Wild poliovirus transmission has never been interrupted in this block due to war against terrorism, poor public health infrastructure, misconceptions about polio vaccines and inadequate immunization activities. All these issues complicate the eradication operations and reinforce the complexity of wiping out poliomyelitis from this region. This study illustrates the origins and routes of cross-border wild poliovirus type 1 (WPV1) transmission during 2010–2012 between Pakistan and Afghanistan. Sequence analyses were conducted based on complete VP1 capsid protein sequences for WPV1 study strains to determine the origin of poliovirus genetic lineages and their evolutionary relationships. Phylogenetic tree was constructed from VP1 gene sequences applying Maximum Likelihood method using Kimura 2- parameter model in MEGA program v 5.0. A total of 72 (14.3%) out of 502 wild-type 1 polioviruses were found circulating in border areas of both countries during 2010–2012. Molecular phylogenetic analysis classified these strains in to two sub-genotypes with four clusters and 18 lineages. Genetic data confirmed that the most of WPV1 lineages (12; 66.6%) were transmitted from Pakistan to Afghanistan. However, the genetic diversity was significantly reduced during 2012 as most of the lineages were completely eliminated. In conclusion, Pakistan-Afghanistan block has emerged as a single poliovirus reservoir sharing the multiple poliovirus lineages due to uncontrolled movement of people across the borders between two countries. If it is neglected, it can jeopardize the extensive global efforts done so-far to eradicate the poliovirus infection. Our data will be helpful to devise the preventive strategies for effective control of wild poliovirus transmission in this region. PMID:25229826

  4. Re-localization of cellular protein SRp20 during poliovirus infection: bridging a viral IRES to the host cell translation apparatus.

    PubMed

    Fitzgerald, Kerry D; Semler, Bert L

    2011-07-01

    Poliovirus IRES-mediated translation requires the functions of certain canonical as well as non-canonical factors for the recruitment of ribosomes to the viral RNA. The interaction of cellular proteins PCBP2 and SRp20 in extracts from poliovirus-infected cells has been previously described, and these two proteins were shown to function synergistically in viral translation. To further define the mechanism of ribosome recruitment for the initiation of poliovirus IRES-dependent translation, we focused on the role of the interaction between cellular proteins PCBP2 and SRp20. Work described here demonstrates that SRp20 dramatically re-localizes from the nucleus to the cytoplasm of poliovirus-infected neuroblastoma cells during the course of infection. Importantly, SRp20 partially co-localizes with PCBP2 in the cytoplasm of infected cells, corroborating our previous in vitro interaction data. In addition, the data presented implicate the presence of these two proteins in viral translation initiation complexes. We show that in extracts from poliovirus-infected cells, SRp20 is associated with PCBP2 bound to poliovirus RNA, indicating that this interaction occurs on the viral RNA. Finally, we generated a mutated version of SRp20 lacking the RNA recognition motif (SRp20ΔRRM) and found that this protein is localized similar to the full length SRp20, and also partially co-localizes with PCBP2 during poliovirus infection. Expression of this mutated version of SRp20 results in a ∼100 fold decrease in virus yield for poliovirus when compared to expression of wild type SRp20, possibly via a dominant negative effect. Taken together, these results are consistent with a model in which SRp20 interacts with PCBP2 bound to the viral RNA, and this interaction functions to recruit ribosomes to the viral RNA in a direct or indirect manner, with the participation of additional protein-protein or protein-RNA interactions.

  5. Molecular characterization and phylogenetic relationship of wild type 1 poliovirus strains circulating across Pakistan and Afghanistan bordering areas during 2010-2012.

    PubMed

    Shaukat, Shahzad; Angez, Mehar; Alam, Muhammad Masroor; Sharif, Salmaan; Khurshid, Adnan; Malik, Farzana; Rehman, Lubna; Zaidi, Syed Sohail Zahoor

    2014-01-01

    Pakistan and Afghanistan share a long uncontrolled border with extensive population movement on both sides. Wild poliovirus transmission has never been interrupted in this block due to war against terrorism, poor public health infrastructure, misconceptions about polio vaccines and inadequate immunization activities. All these issues complicate the eradication operations and reinforce the complexity of wiping out poliomyelitis from this region. This study illustrates the origins and routes of cross-border wild poliovirus type 1 (WPV1) transmission during 2010-2012 between Pakistan and Afghanistan. Sequence analyses were conducted based on complete VP1 capsid protein sequences for WPV1 study strains to determine the origin of poliovirus genetic lineages and their evolutionary relationships. Phylogenetic tree was constructed from VP1 gene sequences applying Maximum Likelihood method using Kimura 2- parameter model in MEGA program v 5.0. A total of 72 (14.3%) out of 502 wild-type 1 polioviruses were found circulating in border areas of both countries during 2010-2012. Molecular phylogenetic analysis classified these strains in to two sub-genotypes with four clusters and 18 lineages. Genetic data confirmed that the most of WPV1 lineages (12; 66.6%) were transmitted from Pakistan to Afghanistan. However, the genetic diversity was significantly reduced during 2012 as most of the lineages were completely eliminated. In conclusion, Pakistan-Afghanistan block has emerged as a single poliovirus reservoir sharing the multiple poliovirus lineages due to uncontrolled movement of people across the borders between two countries. If it is neglected, it can jeopardize the extensive global efforts done so-far to eradicate the poliovirus infection. Our data will be helpful to devise the preventive strategies for effective control of wild poliovirus transmission in this region.

  6. Comparison of ozone inactivation, in flowing water, of hepatitis A virus, poliovirus 1, and indicator organisms

    SciTech Connect

    Herbold, K.; Flehmig, B.; Botzenhart, K. )

    1989-11-01

    In steadily flowing water at 20 degrees C and pH 7, five organisms had the following order of resistance to ozone (at constant levels of ozone): poliovirus 1 (PV1) less than Escherichia coli less than hepatitis A virus (HAV) less than Legionella pneumophila serogroup 6 less than Bacillus subtilis spores. The tests were repeated at 10 degrees C with HAV, PV1, and E. coli. Ozone inactivation of HAV and E. coli was faster at 10 degrees C than at 20 degrees C. At 20 degrees C, 0.25 to 0.38 mg of O3 per liter was required for complete inactivation of HAV but only 0.13 mg of O3 per liter was required for complete inactivation of PV1.

  7. Survival of poliovirus in flowing turbid seawater treated with ultraviolet light.

    PubMed

    Hill, W F; Hamblet, F E; Akin, E W

    1967-05-01

    The effectiveness of a model ultraviolet (UV) radiation unit for treating flowing turbid seawater contaminated with poliovirus was determined. At a turbidity of 70 ppm, the observed survival ratios ranged from 1.9 x 10(-3) (99.81% reduction) to 1.5 x 10(-4) (99.98% reduction) at flow rates ranging from 25 to 15 liters/min; no virus was recovered at flow rates of 10 and 5 liters/min. At a turbidity of 240 ppm, the observed survival ratios ranged from 3.2 x 10(-2) (96.80% reduction) to 2.1 x 10(-4) (99.98% reduction) at flow rates ranging from 25 to 5 liters/min. As expected, turbidity had an adverse influence on the effectiveness of UV radiation; however, by adjusting the flow rate of the seawater through the treatment unit, adequate disinfection was shown to be predictable.

  8. Survival of Poliovirus in Flowing Turbid Seawater Treated with Ultraviolet Light

    PubMed Central

    Hill, W. F.; Hamblet, F. E.; Akin, E. W.

    1967-01-01

    The effectiveness of a model ultraviolet (UV) radiation unit for treating flowing turbid seawater contaminated with poliovirus was determined. At a turbidity of 70 ppm, the observed survival ratios ranged from 1.9 × 10-3 (99.81% reduction) to 1.5 × 10-4 (99.98% reduction) at flow rates ranging from 25 to 15 liters/min; no virus was recovered at flow rates of 10 and 5 liters/min. At a turbidity of 240 ppm, the observed survival ratios ranged from 3.2 × 10-2 (96.80% reduction) to 2.1 × 10-4 (99.98% reduction) at flow rates ranging from 25 to 5 liters/min. As expected, turbidity had an adverse influence on the effectiveness of UV radiation; however, by adjusting the flow rate of the seawater through the treatment unit, adequate disinfection was shown to be predictable. Images Fig. 1 PMID:4291955

  9. Comparison of ozone inactivation, in flowing water, of hepatitis A virus, poliovirus 1, and indicator organisms.

    PubMed Central

    Herbold, K; Flehmig, B; Botzenhart, K

    1989-01-01

    In steadily flowing water at 20 degrees C and pH 7, five organisms had the following order of resistance to ozone (at constant levels of ozone): poliovirus 1 (PV1) less than Escherichia coli less than hepatitis A virus (HAV) less than Legionella pneumophila serogroup 6 less than Bacillus subtilis spores. The tests were repeated at 10 degrees C with HAV, PV1, and E. coli. Ozone inactivation of HAV and E. coli was faster at 10 degrees C than at 20 degrees C. At 20 degrees C, 0.25 to 0.38 mg of O3 per liter was required for complete inactivation of HAV but only 0.13 mg of O3 per liter was required for complete inactivation of PV1. PMID:2560362

  10. 5' termini of poliovirus RNA: difference between virion and nonencapsidated 35S RNA.

    PubMed Central

    Fernandez-Muñoz, R; Lavi, U

    1977-01-01

    Poliovirus cytoplasmic, nonencapsidated 35S RNA yields approximately one pUp per molecule upon T2 RNase digestion, indicating that this RNA has the same 5' end as the polyribosome-associated viral RNA fraction. Double-stranded, replicative form RNA after the same treatment yielded approximately four pNp structures per molecule, 65% of which was pUp. In contrast, the 35S RNA from mature virions contained no detectable pNp, indicating that the 5' end of the virion RNA is different from that of the nonencapsidated RNA. None of the above molecules contained pppNp, ppNp, or GpppNp structures present in host mRNA. The virion RNA molecules, as we have shown previously for thenonencapsidated 35S viral RNA (Fernandez-Muñoz and Darnell, 1976), is not labeled with [methyl-3H]methionine. PMID:189096

  11. Antibody-dependent induction of type I interferons by poliovirus in human mononuclear blood cells requires the type II fcgamma receptor (CD32).

    PubMed

    Palmer, P; Charley, B; Rombaut, B; Daëron, M; Lebon, P

    2000-12-05

    The induction of type I interferons (IFNs) in peripheral blood mononuclear cells (PBMCs) can be triggered by viral infection or exposure to viral glycoproteins. Here we show that the IFN-alpha-inducing capacity of attenuated poliovirus vaccine strains is dramatically enhanced in the presence of human polyvalent immunoglobulin G (IgG). The transcription of both IFN-alpha and IFN-beta genes was detected by RT-PCR in stimulated cells. This antibody-dependent activation of type I IFNs genes was also observed with Formalin-inactivated or UV-inactivated poliovirus, but not with empty poliovirus capsids. The ability of poliovirus-antibody complexes to induce IFN-alpha was specifically inhibited when PBMCs were preincubated with an excess of the Fc fragment of IgG. Monoclonal antibodies directed to FcgammaRII (CD32) were also inhibitory, whereas antibodies to the two other classes of Fcgamma receptors, CD16 and CD64, were not. Also, aggregation of FcgammaRII by anti-CD32 antibodies alone failed to induce IFN-alpha production. Our results suggest that induction of type I interferons by poliovirus-antibody complexes depends on CD32-mediated phagocytosis of RNA-containing viral particles. As suggested by the results of an ELISPOT analysis, only a fraction of the IFN-alpha-producing cells are able to synthesize IFN-alpha in response to poliovirus-IgG complexes.

  12. Prevalence of Asymptomatic Poliovirus Infection in Older Children and Adults in Northern India: Analysis of Contact and Enhanced Community Surveillance, 2009

    PubMed Central

    Mach, Ondrej; Verma, Harish; Khandait, Devendra W.; Sutter, Roland W.; O'Connor, Patrick M.; Pallansch, Mark A.; Cochi, Stephen L.; Linkins, Robert W.; Chu, Susan Y.; Wolff, Chris; Jafari, Hamid S.

    2015-01-01

    Background In 2009, enhanced poliovirus surveillance was established in polio-endemic areas of Uttar Pradesh and Bihar, India, to assess poliovirus infection in older individuals. Methods In Uttar Pradesh, stool specimens from asymptomatic household and neighborhood contacts of patients with laboratory-confirmed polio were tested for polioviruses. In Bihar, in community-based surveillance, children and adults from 250 randomly selected households in the Kosi River area provided stool and pharyngeal swab samples that were tested for polioviruses. A descriptive analysis of surveillance data was performed. Results In Uttar Pradesh, 89 of 1842 healthy contacts of case patients with polio (4.8%) were shedding wild poliovirus (WPV); 54 of 85 (63.5%) were ≥5 years of age. Shedding was significantly higher in index households than in neighborhood households (P < .05). In Bihar, 11 of 451 healthy persons (2.4%) were shedding WPV in their stool; 6 of 11 (54.5%) were ≥5 years of age. Mean viral titer was similar in older and younger children. Conclusions A high proportion of persons ≥5 years of age were asymptomatically shedding polioviruses. These findings provide indirect evidence that older individuals could have contributed to community transmission of WPV in India. Polio vaccination campaigns generally target children <5 years of age. Expanding this target age group in polio-endemic areas could accelerate polio eradication. PMID:25316843

  13. Ala67Thr mutation in the poliovirus receptor CD155 is a potential risk factor for vaccine and wild-type paralytic poliomyelitis.

    PubMed

    Kindberg, Elin; Ax, Cecilia; Fiore, Lucia; Svensson, Lennart

    2009-05-01

    Poliovirus infections can be asymptomatic or cause severe paralysis. Why some individuals develop paralytic poliomyelitis is unknown, but a role for host genetic factors has been suggested. To investigate if a polymorphism, Ala67Thr, in the poliovirus receptor, which has been found to facilitate increased resistance against poliovirus-induced cell lysis and apoptosis, is associated with increased risk of paralytic poliomyelitis, poliovirus receptor genotyping was undertaken among Italian subjects with vaccine-associated (n = 9), or with wild-type paralytic poliomyelitis (n = 6), and control subjects (n = 71), using RFLP-PCR and pyrosequencing. Heterozygous poliovirus receptor Ala67Thr genotype was found in 13.3% of the patients with paresis and in 8.5% of the controls (Odds Ratio = 1.667). The frequency of Ala67Thr among the controls is in agreement with earlier published data. It is concluded that the Ala67Thr mutation in the poliovirus receptor is a possible risk factor for the development of vaccine-associated or paralytic poliomyelitis associated with wild-type virus.

  14. Poliovirus Unlinks TIA1 Aggregation and mRNA Stress Granule Formation▿

    PubMed Central

    White, James P.; Lloyd, Richard E.

    2011-01-01

    In response to environmental stress and viral infection, mammalian cells form foci containing translationally silenced mRNPs termed stress granules (SGs). As aggregates of stalled initiation complexes, SGs are defined by the presence of translation initiation machinery in addition to mRNA binding proteins. Here, we report that cells infected with poliovirus (PV) can form SGs early that contain T-cell-restricted intracellular antigen 1 (TIA1), translation initiation factors, RNA binding proteins, and mRNA. However, this response is blocked as infection progresses, and a type of pseudo-stress granule remains at late times postinfection and contains TIA but lacks translation initiation factors, mRNA binding proteins, and most polyadenylated mRNA. This result was observed using multiple stressors, including viral infection, oxidative stress, heat shock, and endoplasmic reticulum stress. Multiple proteins required for efficient viral internal ribosome entry site-dependent translation are localized to SGs under stress conditions, providing a potential rationale for the evolution and maintenance of the SG inhibition phenotype. Further, the expression of a noncleavable form of the RasGAP-SH3 domain binding protein in PV-infected cells enables SGs whose constituents are consistent with the presence of stalled 48S translation preinitiation complexes to persist throughout infection. These results indicate that in poliovirus-infected cells, the functions of TIA self-aggregation and aggregation of stalled translation initiation complexes into stress granules are severed, leading to novel foci that contain TIA1 but lack other stress granule-defining components. PMID:21957303

  15. Antiviral Activity of Trichilia catigua Bark Extracts for Herpesvirus and Poliovirus.

    PubMed

    Espada, Samantha F; Faccin-Galhardi, Ligia C; Rincao, Vinicius P; Bernardi, Ana L S; Lopes, Nayara; Longhini, Renata; de Mello, Joao C P; Linhares, Rosa E C; Nozawa, Carlos

    2015-01-01

    Herpesvirus and poliovirus are responsible for important diseases in human and animal. Trichilia catigua a Brazilian native plant known as catiguá has several medicinal properties among them antimicrobial for bacteria and protozoa, however, no antiviral activity has been reported yet. This study evaluated the antiviral activity of the crude extract (CE) and aqueous and ethyl acetate fractions (AF, EAF) obtained from T. catigua in the replication of the Herpes simplex virus (HSV-1), bovine herpesvirus (BoHV-1) and poliovirus (PV-1). The cytotoxicity was analyzed by MTT assay and the antiviral effect was determined by the addition of extracts (0.25 to 100.0 μg/ml), before (-2h and -1h), during (Oh) and after (1h and 2h) the viral infection, by plaque reduction assay, in HEp-2 cell culture. The virucidal activity and inhibition of viral adsorption were also evaluated. In addition, the combination index (CI) with Acyclovir (ACV - reference drug) was determined for HSV-1. CE, AF and EAF showed a low toxicity (CC(50) >400 µg/ml) and low inhibitory concentration (IC50), ranging from 2.44-34.25 µg/ml for herpesvirus and 0.67 to 1.8 µg/ml for PV-1, associated with high selectivity index. The tested compounds showed high virucidal effect and high ability to inhibit viral adsorption, for all virus. The CI demonstrated a synergic effect (CI<1) for AF and EAF comparatively to acyclovir (ACV). Our study demonstrated that the extract and fractions of T. catigua is promising for future antiviral drug design with economically feasible production.

  16. Detection and quantification of poliovirus infection using FTIR spectroscopy and cell culture

    PubMed Central

    2011-01-01

    Background In a globalized word, prevention of infectious diseases is a major challenge. Rapid detection of viable virus particles in water and other environmental samples is essential to public health risk assessment, homeland security and environmental protection. Current virus detection methods, especially assessing viral infectivity, are complex and time-consuming, making point-of-care detection a challenge. Faster, more sensitive, highly specific methods are needed to quantify potentially hazardous viral pathogens and to determine if suspected materials contain viable viral particles. Fourier transform infrared (FTIR) spectroscopy combined with cellular-based sensing, may offer a precise way to detect specific viruses. This approach utilizes infrared light to monitor changes in molecular components of cells by tracking changes in absorbance patterns produced following virus infection. In this work poliovirus (PV1) was used to evaluate the utility of FTIR spectroscopy with cell culture for rapid detection of infective virus particles. Results Buffalo green monkey kidney (BGMK) cells infected with different virus titers were studied at 1 - 12 hours post-infection (h.p.i.). A partial least squares (PLS) regression method was used to analyze and model cellular responses to different infection titers and times post-infection. The model performs best at 8 h.p.i., resulting in an estimated root mean square error of cross validation (RMSECV) of 17 plaque forming units (PFU)/ml when using low titers of infection of 10 and 100 PFU/ml. Higher titers, from 103 to 106 PFU/ml, could also be reliably detected. Conclusions This approach to poliovirus detection and quantification using FTIR spectroscopy and cell culture could potentially be extended to compare biochemical cell responses to infection with different viruses. This virus detection method could feasibly be adapted to an automated scheme for use in areas such as water safety monitoring and medical diagnostics. PMID

  17. Spatial Dynamics and High Risk Transmission Pathways of Poliovirus in Nigeria 2001-2013

    PubMed Central

    Mangal, Tara D.; Aylward, R. Bruce; Shuaib, Faisal; Mwanza, Michael; Pate, Muhammed A.; Abanida, Emmanuel; Grassly, Nicholas C.

    2016-01-01

    The polio eradication programme in Nigeria has been successful in reducing incidence to just six confirmed cases in 2014 and zero to date in 2015, but prediction and management of future outbreaks remains a concern. A Poisson mixed effects model was used to describe poliovirus spread between January 2001 and November 2013, incorporating the strength of connectivity between districts (local government areas, LGAs) as estimated by three models of human mobility: simple distance, gravity and radiation models. Potential explanatory variables associated with the case numbers in each LGA were investigated and the model fit was tested by simulation. Spatial connectivity, the number of non-immune children under five years old, and season were associated with the incidence of poliomyelitis in an LGA (all P < 0.001). The best-fitting spatial model was the radiation model, outperforming the simple distance and gravity models (likelihood ratio test P < 0.05), under which the number of people estimated to move from an infected LGA to an uninfected LGA was strongly associated with the incidence of poliomyelitis in that LGA. We inferred transmission networks between LGAs based on this model and found these to be highly local, largely restricted to neighbouring LGAs (e.g. 67.7% of secondary spread from Kano was expected to occur within 10 km). The remaining secondary spread occurred along routes of high population movement. Poliovirus transmission in Nigeria is predominantly localised, occurring between spatially contiguous areas. Outbreak response should be guided by knowledge of high-probability pathways to ensure vulnerable children are protected. PMID:27668435

  18. Continued Endemic Wild Poliovirus Transmission in Security-Compromised Areas - Nigeria, 2016.

    PubMed

    Nnadi, Chimeremma; Damisa, Eunice; Esapa, Lisa; Braka, Fiona; Waziri, Ndadilnasiya; Siddique, Anisur; Jorba, Jaume; Nganda, Gatei Wa; Ohuabunwo, Chima; Bolu, Omotayo; Wiesen, Eric; Adamu, Usman

    2017-02-24

    On August 10, 2016, 2 years after the most recent wild poliovirus (WPV) case was reported in Nigeria (in July 2014) (1), two WPV cases were reported in the northeastern state of Borno, which has been severely affected by insurgency-related insecurity since 2013. On September 9 and 26, 2016, two additional WPV cases were reported in Borno in children whose families migrated from security-compromised, inaccessible areas of the state. All four cases were WPV serotype 1 (WPV1), with genetic differences indicating prolonged undetected transmission. A large-scale emergency response plan was developed and implemented. The plan initially called for vaccination of 815,791 children during August 15-18 in five local government areas (LGAs) in the immediate vicinity of the first two WPV cases. Subsequently, the plan was expanded to regionally synchronized supplementary immunization activities (SIAs), conducted during August 27-December 6 in five Lake Chad basin countries at increased risk for national and regional WPV1 transmission (Cameroon, Central African Republic, Chad, Niger, and Nigeria). In addition, retrospective searches for missed cases of acute flaccid paralysis (AFP), enhanced environmental surveillance for polioviruses, and polio surveillance system reviews were conducted. Prolonged undetected WPV1 transmission in Borno State is a consequence of low population immunity and severe surveillance limitations associated with insurgency-related insecurity and highlights the risk for local and international WPV spread (2). Increasing polio vaccination coverage and implementing high-quality polio surveillance, especially among populations in newly secured and difficult-to-access areas in Borno and other Lake Chad basin areas are urgently needed.

  19. Spatial Dynamics and High Risk Transmission Pathways of Poliovirus in Nigeria 2001-2013.

    PubMed

    Mangal, Tara D; Aylward, R Bruce; Shuaib, Faisal; Mwanza, Michael; Pate, Muhammed A; Abanida, Emmanuel; Grassly, Nicholas C

    The polio eradication programme in Nigeria has been successful in reducing incidence to just six confirmed cases in 2014 and zero to date in 2015, but prediction and management of future outbreaks remains a concern. A Poisson mixed effects model was used to describe poliovirus spread between January 2001 and November 2013, incorporating the strength of connectivity between districts (local government areas, LGAs) as estimated by three models of human mobility: simple distance, gravity and radiation models. Potential explanatory variables associated with the case numbers in each LGA were investigated and the model fit was tested by simulation. Spatial connectivity, the number of non-immune children under five years old, and season were associated with the incidence of poliomyelitis in an LGA (all P < 0.001). The best-fitting spatial model was the radiation model, outperforming the simple distance and gravity models (likelihood ratio test P < 0.05), under which the number of people estimated to move from an infected LGA to an uninfected LGA was strongly associated with the incidence of poliomyelitis in that LGA. We inferred transmission networks between LGAs based on this model and found these to be highly local, largely restricted to neighbouring LGAs (e.g. 67.7% of secondary spread from Kano was expected to occur within 10 km). The remaining secondary spread occurred along routes of high population movement. Poliovirus transmission in Nigeria is predominantly localised, occurring between spatially contiguous areas. Outbreak response should be guided by knowledge of high-probability pathways to ensure vulnerable children are protected.

  20. Characterization of Poliovirus Neutralization Escape Mutants of Single-Domain Antibody Fragments (VHHs)

    PubMed Central

    Schotte, Lise; Thys, Bert; Strauss, Mike; Filman, David J.; Rombaut, Bart

    2015-01-01

    To complete the eradication of poliovirus and to protect unvaccinated people subsequently, the development of one or more antiviral drugs will be necessary. A set of five single-domain antibody fragments (variable parts of the heavy chain of a heavy-chain antibody [VHHs]) with an in vitro neutralizing activity against poliovirus type 1 was developed previously (B. Thys, L. Schotte, S. Muyldermans, U. Wernery, G. Hassanzadeh-Ghassabeh, and B. Rombaut, Antiviral Res 87:257–264, 2010, http://dx.doi.org/10.1016/j.antiviral.2010.05.012), and their mechanisms of action have been studied (L. Schotte, M. Strauss, B. Thys, H. Halewyck, D. J. Filman, M. Bostina, J. M. Hogle, and B. Rombaut, J Virol 88:4403–4413, 2014, http://dx.doi.org/10.1128/JVI.03402-13). In this study, neutralization escape mutants were selected for each VHH. Sequencing of the P1 region of the genome showed that amino acid substitutions are found in the four viral proteins of the capsid and that they are located both in proximity to the binding sites of the VHHs and in regions further away from the canyon and hidden beneath the surface. Characterization of the mutants demonstrated that they have single-cycle replication kinetics that are similar to those of their parental strain and that they are all drug (VHH) independent. Their resistant phenotypes are stable, as they do not regain full susceptibility to the VHH after passage over HeLa cells in the absence of VHH. They are all at least as stable as the parental strain against heat inactivation at 44°C, and three of them are even significantly (P < 0.05) more resistant to heat inactivation. The resistant variants all still can be neutralized by at least two other VHHs and retain full susceptibility to pirodavir and 35-1F4. PMID:26014941

  1. Poliovirus unlinks TIA1 aggregation and mRNA stress granule formation.

    PubMed

    White, James P; Lloyd, Richard E

    2011-12-01

    In response to environmental stress and viral infection, mammalian cells form foci containing translationally silenced mRNPs termed stress granules (SGs). As aggregates of stalled initiation complexes, SGs are defined by the presence of translation initiation machinery in addition to mRNA binding proteins. Here, we report that cells infected with poliovirus (PV) can form SGs early that contain T-cell-restricted intracellular antigen 1 (TIA1), translation initiation factors, RNA binding proteins, and mRNA. However, this response is blocked as infection progresses, and a type of pseudo-stress granule remains at late times postinfection and contains TIA but lacks translation initiation factors, mRNA binding proteins, and most polyadenylated mRNA. This result was observed using multiple stressors, including viral infection, oxidative stress, heat shock, and endoplasmic reticulum stress. Multiple proteins required for efficient viral internal ribosome entry site-dependent translation are localized to SGs under stress conditions, providing a potential rationale for the evolution and maintenance of the SG inhibition phenotype. Further, the expression of a noncleavable form of the RasGAP-SH3 domain binding protein in PV-infected cells enables SGs whose constituents are consistent with the presence of stalled 48S translation preinitiation complexes to persist throughout infection. These results indicate that in poliovirus-infected cells, the functions of TIA self-aggregation and aggregation of stalled translation initiation complexes into stress granules are severed, leading to novel foci that contain TIA1 but lack other stress granule-defining components.

  2. Inactivation of Ascaris suum and poliovirus in biosolids under thermophilic anaerobic digestion conditions.

    PubMed

    Aitken, Michael D; Sobsey, Mark D; Blauth, Kimberly E; Shehee, Mina; Crunk, Phillip L; Walters, Glenn W

    2005-08-01

    There is considerable interest in the United States in production of Class A (low pathogen content) biosolids from the treatment of municipal wastewater sludge. Current requirements imposed by the U.S. Environmental Protection Agency make it difficult for thermophilic anaerobic digestion, in its simplest process configurations, to achieve Class A status. In particular, the time-temperature requirements necessitate long batch treatment times at temperatures associated with thermophilic anaerobic digestion. The time-temperature requirements are meant to ensure extensive inactivation of helminth eggs and enteric viruses, considered to be the most heat-resistant of the relevant pathogen classes. However, data on inactivation kinetics of these pathogens at precisely controlled and well-characterized temperatures are scarce. We measured inactivation of vaccine-strain poliovirus and eggs from the helminth Ascaris suum at temperatures from 49 to 55 degrees C in a lab-scale batch reactor containing biosolids from a continuous-flow thermophilic anaerobic digester. Both microbes were inactivated rapidly, with Ascaris more resistant to inactivation than poliovirus, and the relationships between inactivation rate and temperature were steep. The Arrhenius correlation between inactivation rate and temperature over the range 49-53 degrees C is consistent with protein denaturation as the inactivation mechanism for both microbes. The least stringent of the EPA time-temperature equations for thermal processes requires batch treatment times more than 2 orders of magnitude greater than would be required for three-log reduction of Ascaris at the rates we measured, suggesting an overly conservative regulatory approach. Such a grossly conservative approach can hinder full-scale implementation of thermophilic anaerobic digestion.

  3. Immunodeficiency-related vaccine-derived poliovirus (iVDPV) cases: a systematic review and implications for polio eradication.

    PubMed

    Guo, Jean; Bolivar-Wagers, Sara; Srinivas, Nivedita; Holubar, Marisa; Maldonado, Yvonne

    2015-03-03

    Vaccine-derived polioviruses (VDPVs), strains of poliovirus mutated from the oral polio vaccine, pose a challenge to global polio eradication. Immunodeficiency-related vaccine-derived polioviruses (iVDPVs) are a type of VDPV which may serve as sources of poliovirus reintroduction after the eradication of wild-type poliovirus. This review is a comprehensive update of confirmed iVDPV cases published in the scientific literature from 1962 to 2012, and describes clinically relevant trends in reported iVDPV cases worldwide. We conducted a systematic review of published iVDPV case reports from January 1960 to November 2012 from four databases. We included cases in which the patient had a primary immunodeficiency, and the vaccine virus isolated from the patient either met the sequencing definition of VDPV (>1% divergence for serotypes 1 and 3 and >0.6% for serotype 2) and/or was previously reported as an iVDPV by the World Health Organization. We identified 68 iVDPV cases in 49 manuscripts reported from 25 countries and the Palestinian territories. 62% of case patients were male, 78% presented clinically with acute flaccid paralysis, and 65% were iVDPV2. 57% of cases occurred in patients with predominantly antibody immunodeficiencies, and the overall all-cause mortality rate was greater than 60%. The median age at case detection was 1.4 years [IQR: 0.8, 4.5] and the median duration of shedding was 1.3 years [IQR: 0.7, 2.2]. We identified a poliovirus genome VP1 region mutation rate of 0.72% per year and a higher median percent divergence for iVDPV1 cases. More cases were reported from high income countries, which also had a larger age variation and different distribution of immunodeficiencies compared to upper and lower middle-income countries. Our study describes the incidence and characteristics of global iVDPV cases reported in the literature in the past five decades. It also highlights the regional and economic disparities of reported iVDPV cases. Copyright © 2015

  4. Efficacy of Nucleic Acid Probes for Detection of Poliovirus in Water Disinfected by Chlorine, Chlorine Dioxide, Ozone, and UV Radiation

    PubMed Central

    Moore, Norman J.; Margolin, Aaron B.

    1994-01-01

    MilliQ water was inoculated with poliovirus type 1 strain LSc-1 and was treated with disinfectants, including chlorine, chlorine dioxide, ozone, and UV light. No relationship between probes and plaque assays were seen, demonstrating that viral nucleic acids were not destroyed. These findings suggest that nucleic acid probes cannot distinguish between infectious and noninfectious viruses and cannot be used in the evaluation of treated waters. PMID:16349448

  5. Viral aggregation: buffer effects in the aggregation of poliovirus and reovirus at low and high pH.

    PubMed Central

    Floyd, R; Sharp, D G

    1979-01-01

    The effects of the buffer employed in maintaining a given pH value were tested on the aggregation of two viruses, poliovirus and reovirus. Poliovirus was found to aggregate at pH values of 6 and below, but not at pH 7 or above, except in borate buffer. Reovirus aggregated at pH 4 and below, but was found to aggregate only in acetate or tris(hydroxymethyl)aminomethane-citrate buffers at pH 5. Other buffers tested for aggregation of reovirus at pH 5 (succinate, citrate, and phosphate-citrate) induced little aggregation. No significant aggregation was found for reovirus at pH 6 and above. For both viruses, the most effective aggregation was induced by buffers having a substantial monovalently charged anionic component, such as acetate at pH 5 and 6 or citrate at pH 3. Cationic buffers at low pH, such as glycine, were generally weaker in aggregating ability than anionic buffers at the same pH. These results, when correlated with the isoelectric point of the viruses (poliovirus at pH 8.2; reovirus at pH 3.9) indicated that both viruses aggregated strongly when their overall charge was positive, but only under certain circumstances when their overall charge was negative. Although reovirus aggregated massively at its isoelectric point, poliovirus remained dispersed at its isoelectric point. The conclusion can be drawn that those pH and buffer conditions which induced aggregation of one virus do not necessarily induce it in another. PMID:43706

  6. Proteolytic processing of poliovirus polypeptides: antibodies to polypeptide P3-7c inhibit cleavage at glutamine-glycine pairs

    SciTech Connect

    Hanecak, R.; Semler, B.L.; Anderson, C.W.; Wimmer, E.

    1982-07-01

    Proteolytic processing of poliovirus polypeptides was examined by the addition of antibodies directed against the viral proteins P3-7c and P2-X to a cell-free translation extract prepared from infected HeLa cells. Antisera to P3-7c specifically inhibited in vitro processing at Gln-Gly pairs. Partial amino acid sequence analysis revealed a second Tyr-Gly pair that is utilized in protein processing. Neither Tyr-Gly cleavage is affected by antibody to P3-7C. Anti-P3-7c antibodies react not only with P3-7c but also with P3-6a and P3-2, two viral polypeptides NH/sub 2/-coterminal with P3-7c. Preimmune and anti-P2-X antibodies had no effect on the processing of poliovirus proteins in vitro. The authors conclude that the activity responsible for processing poliovirus polypeptides at Gln-Gly pairs resides in the primary structure of P3-7c and not in P2-X.

  7. Poliovirus replication proteins: RNA sequence encoding P3-1b and the sites of proteolytic processing

    SciTech Connect

    Semler, B.L.; Anderson, C.W.; Kitamura, N.; Rothberg, P.G.; Wishart, W.L.; Wimmer, E.

    1981-06-01

    A partial amino-terminal amino acid sequence of each of the major proteins encoded by the replicase region of the poliovirus genome has been determined. A comparison of this sequence information with the amino acid sequence predicted from the RNA sequence that has been determined for the 3' region of the poliovirus genome has allowed us to locate precisely the proteolytic cleavage sites at which the initial polyprotein is processed to create the poliovirus products P3-1b (NCVP1b), P3-2 (NCVP2), P3-4b (NCVP4b), and P3-7c (NCVP7c). For each of these products, as well as for the small genome-linked protein VPg, proteolytic cleavage occurs between a glutamine and a glycine residue to create the amino terminus of each protein. This result suggests that a single proteinase may be responsible for all of these cleavages. The sequence data also allow the precise positioning of the genome-linked protein VPg within the precursor P3-1b just proximal to the amino terminus of polypeptide P3-2.

  8. MicroRNA screening identifies miR-134 as a regulator of poliovirus and enterovirus 71 infection

    PubMed Central

    Orr-Burks, Nichole Lynn; Shim, Byoung-Shik; Wu, Weilin; Bakre, Abhijeet A.; Karpilow, Jon; Tripp, Ralph A.

    2017-01-01

    MicroRNAs (miRNAs) regulate virus replication through multiple mechanisms. Poliovirus causes a highly debilitating disease and though global efforts to eradicate polio have sharply decreased polio incidence, unfortunately three countries (Afghanistan, Nigeria and Pakistan) remain polio-endemic. We hypothesize that understanding the host factors involved in polio replication will identify novel prophylactic and therapeutic targets against polio and related viruses. In this data set, employing genome wide screens of miRNA mimics and inhibitors, we identified miRNAs which significantly suppressed polio replication. Specifically, miR-134 regulates poliovirus replication via modulation of ras-related nuclear protein (RAN), an important component of the nuclear transport system. MiR-134 also inhibited other Picornaviridae viruses including EV71, a growing concern and a high priority for vaccination in Asian countries like China. These findings demonstrate a novel mechanism for miRNA regulation of poliovirus and other Picornaviridae viruses in host cells, and thereby may provide a novel approach in combating infection and a potential approach for the development of anti-Picornaviridae strategies. PMID:28248924

  9. A stable HeLa cell line that inducibly expresses poliovirus 2A(pro): effects on cellular and viral gene expression.

    PubMed

    Barco, A; Feduchi, E; Carrasco, L

    2000-03-01

    A HeLa cell clone (2A7d) that inducibly expresses the gene for poliovirus protease 2A (2A(pro)) under the control of tetracycline has been obtained. Synthesis of 2A(pro) induces severe morphological changes in 2A7d cells. One day after tetracycline removal, cells round up and a few hours later die. Poliovirus 2A(pro) cleaves both forms of initiation factor eIF4G, causing extensive inhibition of capped-mRNA translation a few hours after protease induction. Methoxysuccinyl-Ala-Ala-Pro-Val-chloromethylketone, a selective inhibitor of 2A(pro), prevents both eIF4G cleavage and inhibition of translation but not cellular death. Expression of 2A(pro) still allows both the replication of poliovirus and the translation of mRNAs containing a picornavirus leader sequence, while vaccinia virus replication is drastically inhibited. Translation of transfected capped mRNA is blocked in 2A7d-On cells, while luciferase synthesis from a mRNA bearing a picornavirus internal ribosome entry site (IRES) sequence is enhanced by the presence of 2A(pro). Moreover, synthesis of 2A(pro) in 2A7d cells complements the translational defect of a poliovirus 2A(pro)-defective variant. These results show that poliovirus 2A(pro) expression mimics some phenotypical characteristics of poliovirus-infected cells, such as cell rounding, inhibition of protein synthesis and enhancement of IRES-driven translation. This cell line constitutes a useful tool to further analyze 2A(pro) functions, to complement poliovirus 2A(pro) mutants, and to test antiviral compounds.

  10. Inactivated poliovirus vaccine given alone or in a sequential schedule with bivalent oral poliovirus vaccine in Chilean infants: a randomised, controlled, open-label, phase 4, non-inferiority study.

    PubMed

    O'Ryan, Miguel; Bandyopadhyay, Ananda S; Villena, Rodolfo; Espinoza, Mónica; Novoa, José; Weldon, William C; Oberste, M Steven; Self, Steve; Borate, Bhavesh R; Asturias, Edwin J; Clemens, Ralf; Orenstein, Walter; Jimeno, José; Rüttimann, Ricardo; Costa Clemens, Sue Ann

    2015-11-01

    Bivalent oral poliovirus vaccine (bOPV; types 1 and 3) is expected to replace trivalent OPV (tOPV) globally by April, 2016, preceded by the introduction of at least one dose of inactivated poliovirus vaccine (IPV) in routine immunisation programmes to eliminate vaccine-associated or vaccine-derived poliomyelitis from serotype 2 poliovirus. Because data are needed on sequential IPV-bOPV schedules, we assessed the immunogenicity of two different IPV-bOPV schedules compared with an all-IPV schedule in infants. We did a randomised, controlled, open-label, non-inferiority trial with healthy, full-term (>2·5 kg birthweight) infants aged 8 weeks (± 7 days) at six well-child clinics in Santiago, Chile. We used supplied lists to randomly assign infants (1:1:1) to receive three polio vaccinations (IPV by injection or bOPV as oral drops) at age 8, 16, and 24 weeks in one of three sequential schedules: IPV-bOPV-bOPV, IPV-IPV-bOPV, or IPV-IPV-IPV. We did the randomisation with blocks of 12 stratified by study site. All analyses were done in a masked manner. Co-primary outcomes were non-inferiority of the bOPV-containing schedules compared with the all-IPV schedule for seroconversion (within a 10% margin) and antibody titres (within two-thirds log2 titres) to poliovirus serotypes 1 and 3 at age 28 weeks, analysed in the per-protocol population. Secondary outcomes were seroconversion and titres to serotype 2 and faecal shedding for 4 weeks after a monovalent OPV type 2 challenge at age 28 weeks. Safety analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01841671, and is closed to new participants. Between April 25 and August 1, 2013, we assigned 570 infants to treatment: 190 to IPV-bOPV-bOPV, 192 to IPV-IPV-bOPV, and 188 to IPV-IPV-IPV. 564 (99%) were vaccinated and included in the intention-to-treat cohort, and 537 (94%) in the per-protocol analyses. In the IPV-bOPV-bOPV, IPV-IPV-bOPV, and IPV-IPV-IPV groups

  11. [Seroprevalence of antibodies to measles, rubella, mumps, hepatitis B viruses and all three poliovirus serotypes among children in Quindío, Colombia].

    PubMed

    González, María M; Sarmiento, Luis; Giraldo, Alejandra M; Padilla, Leonardo; Rey-Benito, Gloria; Castaño, Jhon C

    2016-02-01

    Objective The main goal of this research was to assess the seroprevalence of antibodies against measles, rubella, mumps, hepatitis B and all three poliovirus serotypes among children in the Quindío Department, Colombia. Methods Blood samples were obtained from 170 healthy children aged 5-9 years from nine municipalities in Quindío. The presence of serum IgG antibodies against measles, rubella, mumps and Hepatitis B were determined using commercial indirect ELISA kits. Immunity to poliomyelitis was assessed through the presence of neutralizing antibodies following the method recommended by the World Health Organization. Results Among the 170 children enrolled, 169 (99.41%), 170 (100 %), and 167 (98.2 %) were seropositive to poliovirus 1, poliovirus 2, and poliovirus 3, respectively. The average reciprocal antibody titers were 178 for poliovirus type 1, 120 for type 2 and 56 for type 3. Of the 170 children, 96.47 % were protected against mumps and rubella, and 86.47 % against measles. Only 106 (62.35 %) of the studied subjects were proved to be seropositive to hepatitis B. Conclusion The immunization program in Quindío has provided seroprotection against all three poliomyelitis serotypes, rubella and mumps. However, the child population is not fully protected against measles and hepatitis B virus infections.

  12. Poliovirus genome RNA hybridizes specifically to higher eukaryotic rRNAs.

    PubMed Central

    McClure, M A; Perrault, J

    1985-01-01

    The RNA genome of poliovirus hybridizes to 28S and 18S rRNAs of higher eukaryotes under stringent conditions. The hybridization detected by Northern blot analyses is specific since little or no signal was detected for yeast or prokaryotic rRNAs or other major cellular RNAs. Southern blot analysis of DNA clones of mouse rRNA genes leads us to conclude that several regions of 28S rRNA, and at least one region in 18S rRNA, are involved in the hybridization to polio RNA, and that G/C regions are not responsible for this phenomenon. We have precisely mapped one of these hybridizing regions in both molecules. Computer analysis confirms that extensive intermolecular base-pairing (81 out of 104 contiguous bases in the rRNA strand) could be responsible for this one particular site of interaction (polio genome, bases 5075-5250; 28S rRNA, bases 1097-1200). We discuss the possible functional and/or evolutionary significance of this novel type of interaction. Images PMID:2997728

  13. Reduction of Norwalk virus, poliovirus 1, and bacteriophage MS2 by ozone disinfection of water.

    PubMed

    Shin, Gwy-Am; Sobsey, Mark D

    2003-07-01

    Norwalk virus and other human caliciviruses (noroviruses) are major agents of gastroenteritis, and water is a major route of their transmission. In an effort to control Norwalk virus in drinking water, Norwalk virus reduction by bench-scale ozone disinfection was determined using quantitative reverse transcription (RT)-PCR for virus assays. Two other enteric viruses, poliovirus 1 and coliphage MS2, were included for comparison, and their reductions were assayed by infectivity assays as well as by RT-PCR. Virus reductions by ozone were determined using a dose of 0.37 mg of ozone/liter at pH 7 and 5 degrees C for up to 5 min. Based on two RT-PCR assays, the reductions of Norwalk virus were >3 log(10) within a contact time of 10 s, and these were similar to the reductions of the other two viruses determined by the same assay methods. Also, the virus reductions detected by RT-PCR assays were similar to those detected by infectivity assays, indicating that the RT-PCR assay is a reliable surrogate assay for both culturable and nonculturable viruses disinfected with ozone. Overall, the results of this study indicate that Norwalk virus as well as other enteric viruses can be reduced rapidly and extensively by ozone disinfection and that RT-PCR is a useful surrogate assay for both culturable and nonculturable viruses disinfected with ozone.

  14. Oncolytic Immunotherapy Through Tumor-specific Translation and Cytotoxicity of Poliovirus

    PubMed Central

    Brown, Michael C.; Gromeier, Matthias

    2016-01-01

    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. PMID:26105699

  15. Improved poliovirus D-antigen yields by application of different Vero cell cultivation methods.

    PubMed

    Thomassen, Yvonne E; Rubingh, Olaf; Wijffels, René H; van der Pol, Leo A; Bakker, Wilfried A M

    2014-05-19

    Vero cells were grown adherent to microcarriers (Cytodex 1; 3 g L(-1)) using animal component free media in stirred-tank type bioreactors. Different strategies for media refreshment, daily media replacement (semi-batch), continuous media replacement (perfusion) and recirculation of media, were compared with batch cultivation. Cell densities increased using a feed strategy from 1×10(6) cells mL(-1) during batch cultivation to 1.8, 2.7 and 5.0×10(6) cells mL(-1) during semi-batch, perfusion and recirculation, respectively. The effects of these different cell culture strategies on subsequent poliovirus production were investigated. Increased cell densities allowed up to 3 times higher D-antigen levels when compared with that obtained from batch-wise Vero cell culture. However, the cell specific D-antigen production was lower when cells were infected at higher cell densities. This cell density effect is in good agreement with observations for different cell lines and virus types. From the evaluated alternative culture methods, application of a semi-batch mode of operations allowed the highest cell specific D-antigen production. The increased product yields that can easily be reached using these higher cell density cultivation methods, showed the possibility for better use of bioreactor capacity for the manufacturing of polio vaccines to ultimately reduce vaccine cost per dose. Further, the use of animal-component-free cell- and virus culture media shows opportunities for modernization of human viral vaccine manufacturing.

  16. Transmission dynamics of oral polio vaccine viruses and vaccine-derived polioviruses on networks.

    PubMed

    Kim, Jong-Hoon; Rho, Seong-Hwan

    2015-01-07

    One drawback of oral polio vaccine (OPV) is the potential reversion to more transmissible, virulent circulating vaccine-derived polioviruses (cVDPVs), which may cause outbreaks of paralytic poliomyelitis. Previous modeling studies of the transmission of cVDPVs assume an unrealistic homogeneous mixing of the population and/or ignore that OPV viruses and cVDPVs compete for susceptibles, which we show is a key to understanding the dynamics of the transmission of cVDPVs. We examined the transmission of OPV viruses and cVDPVs on heterogeneous, dynamic contact networks using differential equation-based and individual-based models. Despite the lower transmissibility, OPV viruses may outcompete more transmissible cVDPVs in the short run by spreading extensively before cVDPVs emerge. If viruses become endemic, however, cVDPVs eventually dominate and force OPV viruses to extinction. This study improves our understanding of the emergence of cVDPVs and helps develop more detailed models to plan a policy to control paralytic polio associated with the continued use of OPV in many countries.

  17. Effects of bentonite clay solids on poliovirus concentration from water by microporous filter methods.

    PubMed Central

    Sobsey, M D; Cromeans, T

    1985-01-01

    To determine whether suspended solids interfere with enteric virus recovery from water by microporous filter methods, the effects of bentonite clay solids at a concentration of 10 nephelometric turbidity units on the recovery of poliovirus type 1 from seeded, activated carbon-treated, filtered tap water were studied. Volumes (500 ml) of virus-laden water at pH 5.5 or 7.5, with and without 50 mM MgCl2, were filtered through 47-mm-diameter, electropositive (Virosorb 1MDS) and electronegative (Filterite) filters that had been pretreated with Tween 80 to minimize direct virus adsorption to filter surfaces. Bentonite solids enhanced virus retention on both types of filters, even under conditions in which viruses were not solids associated. However, bentonite solids also interfered with elution of retained viruses when eluting with 0.3% beef extract-50 mM glycine (pH 9.5). Under some conditions, overall virus recoveries were lower from water with bentonite solids than from solids-free control water. The results of this study indicate that clay turbidity can interfere somewhat with virus recovery by current microporous filter methods. PMID:2988438

  18. Molecular characterization of a wild poliovirus type 3 epidemic in The Netherlands (1992 and 1993).

    PubMed Central

    Mulders, M N; van Loon, A M; van der Avoort, H G; Reimerink, J H; Ras, A; Bestebroer, T M; Drebot, M A; Kew, O M; Koopmans, M P

    1995-01-01

    An outbreak of poliomyelitis due to wild poliovirus type 3 (PV3) occurred in an unvaccinated community in The Netherlands between September 1992 and February 1993. The outbreak involved 71 patients. The aim of this study was to characterize the virus at the molecular level and to analyze the molecular evolution of the epidemic virus. Molecular analysis was carried out by sequencing the VP1/2A junction region (150 nucleotides) of 50 PV3 strains isolated in association with this outbreak and the entire VP1 gene of 14 strains. In addition, the sequence of the VP1/2A junction region of strains from geographical regions endemic for PV3 (Egypt, India, and Central Asia) was analyzed and compared with the nucleotide sequence of the epidemic strain from The Netherlands. The earliest isolate was obtained from river water sampled 3 weeks before diagnosis of the first poliomyelitis patient and was found by VP1/2A sequence analysis to be genetically identical to the strain isolated from the first patient. Sequence divergence among the strains from the epidemic in The Netherlands was less than 2%. The closest genetic similarity (97.3%) was found with an Indian isolate (New Delhi, December 1991), indicating the likely source of the virus. A more than 99% sequence similarity was found in the VP1/2A region. Finally, the sequence information was used to design primers for the specific and highly sensitive molecular detection of PV3 strains during the epidemic. PMID:8586711

  19. Crystal structure of CD155 and electron microscopic studies of its complexes with polioviruses.

    PubMed

    Zhang, Ping; Mueller, Steffen; Morais, Marc C; Bator, Carol M; Bowman, Valorie D; Hafenstein, Susan; Wimmer, Eckard; Rossmann, Michael G

    2008-11-25

    When poliovirus (PV) recognizes its receptor, CD155, the virus changes from a 160S to a 135S particle before releasing its genome into the cytoplasm. CD155 is a transmembrane protein with 3 Ig-like extracellular domains, D1-D3, where D1 is recognized by the virus. The crystal structure of D1D2 has been determined to 3.5-A resolution and fitted into approximately 8.5-A resolution cryoelectron microscopy reconstructions of the virus-receptor complexes for the 3 PV serotypes. These structures show that, compared with human rhinoviruses, the virus-receptor interactions for PVs have a greater dependence on hydrophobic interactions, as might be required for a virus that can inhabit environments of different pH. The pocket factor was shown to remain in the virus during the first recognition stage. The present structures, when combined with earlier mutational investigations, show that in the subsequent entry stage the receptor moves further into the canyon when at a physiological temperature, thereby expelling the pocket factor and separating the viral subunits to form 135S particles. These results provide a detailed analysis of how a nonenveloped virus can enter its host cell.

  20. Poliovirus receptor (CD155) regulates a step in transendothelial migration between PECAM and CD99.

    PubMed

    Sullivan, David P; Seidman, Michael A; Muller, William A

    2013-03-01

    The movement of leukocytes across endothelium [referred to as diapedesis or transendothelial migration (TEM)] is a critical step in the inflammatory process. Recently, it was demonstrated that treatment of endothelial cells and monocytes with antibodies against poliovirus receptor (PVR; CD155) and DNAX-associated molecule-1 (DNAM-1; CD226) arrested monocytes over endothelial junctions and prevented TEM, suggesting that these molecules are involved in diapedesis. However, nothing was known about the mechanism by which PVR and DNAM-1 work in TEM. Herein, we show that, similar to endothelial PECAM interacting with leukocyte PECAM, activation of endothelial PVR with anti-PVR antibodies or interaction with its ligand, DNAM-1, results in recruitment of the tyrosine phosphatase Shp-2, and this process is dependent on Src kinases. Furthermore, differential and sequential treatment with blocking antibodies directed against PVR, DNAM-1, PECAM, and CD99 showed that endothelial PVR and monocyte DNAM-1 interact at and regulate a step between those regulated by PECAM and CD99. Further studies demonstrate that PVR resides in the recently identified lateral border recycling compartment, similar to PECAM and CD99. These findings suggest that the localization of adhesion/signaling molecules to the lateral border recycling compartment and the recruitment of Shp-2 may be common mechanisms for the regulation of TEM by endothelial cells.

  1. Amiloride inhibits the initiation of Coxsackievirus and poliovirus RNA replication by inhibiting VPg uridylylation.

    PubMed

    Ogram, Sushma A; Boone, Christopher D; McKenna, Robert; Flanegan, James B

    2014-09-01

    The mechanism of amiloride inhibition of Coxsackievirus B3 (CVB3) and poliovirus type 1 (PV1) RNA replication was investigated using membrane-associated RNA replication complexes. Amiloride was shown to inhibit viral RNA replication and VPgpUpU synthesis. However, the drug had no effect on polymerase elongation activity during either (-) strand or (+) strand synthesis. These findings indicated that amiloride inhibited the initiation of RNA synthesis by inhibiting VPg uridylylation. In addition, in silico binding studies showed that amiloride docks in the VPg binding site on the back of the viral RNA polymerase, 3D(pol). Since VPg binding at this site on PV1 3D(pol) was previously shown to be required for VPg uridylylation, our results suggest that amiloride inhibits VPg binding to 3D(pol). In summary, our findings are consistent with a model in which amiloride inhibits VPgpUpU synthesis and viral RNA replication by competing with VPg for binding to 3D(pol).

  2. MS-2 and poliovirus transport in porous media: Hydrophobic effects and chemical perturbations

    NASA Astrophysics Data System (ADS)

    Bales, Roger C.; Li, Shimin; Maguire, Kimberly M.; Yahya, Moyasar T.; Gerba, Charles P.

    1993-04-01

    In a series of pH 7 continuous-flow column experiments, removal of the bacteriophage MS-2 by attachment to silica beads had a strong, systematic dependence on the amount of hydrophobic surface present on the beads. With no hydrophobic surface, removal of phage at pH 5 was much greater than at pH 7. Release of attached phage at both pH values did occur, but was slow; breakthrough curves exhibited tailing. Poliovirus attached to silica beads at pH 5.5 much more than at pH 7.0, and attachment was also slowly reversible. Time scales for phage and poliovinis attachment were of the order of hours. The sticking efficiency factor (α), reflecting microscaie physicochemical influences on virus attachment, was in the range of 0.0007-0.02. Phage release was small but measurable under steady state conditions. Release was enhanced by lowering ionic strength and by introducing beef extract, a high-ionic-strength protein solution. Results show that viruses experience reversible attachment/detachment (sometimes termed sorption), that large chemical perturbations are needed to induce rapid virus detachment, and that viruses should be quite mobile in sandy porous media. Even small amounts of hydrophobic organic material in the porous media (≥0.001%) can retard virus transport.

  3. Efficiency of several micro-fiber glass filters for recovery of poliovirus from tape water.

    PubMed Central

    Payment, P; Trudel, M

    1979-01-01

    Micro-fiber glass filters from Gelman, Filterite, Johns-Manville, and Whatman were compared with Millipore membrane filters on the basis of their virus adsorbancy, flow rate, clogging resistance, and virus concentration efficiency by using tap water at 2 nephelometric turbidity units. As virus adsorbants the Johns-Manville D39, Filterite 0.25-micron, Filterite 0.45-micron, and Millipore 0.45-micron filters were the most efficient, retaining more than 99% of the added virus in water at pH 3.5 and 0.0005 M aluminum chloride. The Johns-Manville D79 and D49 filters retained 92 and 96% of the virus, respectively, whereas the Whatman GF-D, Whatman GF-F, Gelman A-E, and Millipore AP-20 filters retained only 28, 78, 56, and 34% of the virus, respectively. The best flow rate and clogging resistance were obtained with the Johns-Manville D79 filter or with this filter acting as a prefilter to the Johns-Manville D49, Johns-Manville D39, or Filterite 0.45-micron filter. Finally, poliovirus experimentally seeded in 20 liters of tape water was recovered from Johns-Manville D79-Johns-Manville D39 or Johns-Manville D79-Filterite 0.45 micron 142-mm filter combinations was a efficiencies of 86 and 85%, respectively. PMID:231414

  4. Cellular COPII Proteins Are Involved in Production of the Vesicles That Form the Poliovirus Replication Complex

    PubMed Central

    Rust, René C.; Landmann, Lukas; Gosert, Rainer; Tang, Bor Luen; Hong, Wanjin; Hauri, Hans-Peter; Egger, Denise; Bienz, Kurt

    2001-01-01

    Poliovirus (PV) replicates its genome in association with membranous vesicles in the cytoplasm of infected cells. To elucidate the origin and mode of formation of PV vesicles, immunofluorescence labeling with antibodies against the viral vesicle marker proteins 2B and 2BC, as well as cellular markers of the endoplasmic reticulum (ER), anterograde transport vesicles, and the Golgi complex, was performed in BT7-H cells. Optical sections obtained by confocal laser scanning microscopy were subjected to a deconvolution process to enhance resolution and signal-to-noise ratio and to allow for a three-dimensional representation of labeled membrane structures. The mode of formation of the PV vesicles was, on morphological grounds, similar to the formation of anterograde membrane traffic vesicles in uninfected cells. ER-resident membrane markers were excluded from both types of vesicles, and the COPII components Sec13 and Sec31 were both found to be colocalized on the vesicular surface, indicating the presence of a functional COPII coat. PV vesicle formation during early time points of infection did not involve the Golgi complex. The expression of PV protein 2BC or the entire P2 and P3 genomic region led to the production of vesicles carrying a COPII coat and showing the same mode of formation as vesicles produced after PV infection. These results indicate that PV vesicles are formed at the ER by the cellular COPII budding mechanism and thus are homologous to the vesicles of the anterograde membrane transport pathway. PMID:11559814

  5. Polypeptide composition of urea- and heat-resistant mutants of poliovirus types 1 and 2.

    PubMed

    Fennell, R; Phillips, B A

    1974-10-01

    Five urea-resistant and two heat-resistant mutants of poliovirus types 1 and 2 were isolated and their structural and nonstructural polypeptides compared to those of their wild-type, parental strains in an attempt to correlate mutant phenotypes with alterations in specific capsid polypeptides. Four of the seven mutants were found to contain polypeptides which differed in molecular weight from their respective parental viruses. However, resistance of virions to heat- or urea-inactivation could not be attributed to changes in particular capsid polypeptides because alterations were detected in all but one of the capsid components. For two of the urea-resistant mutants and one heat-resistant mutant, no differences were found in the molecular weights of the capsid and noncapsid polypeptides. These results, and the fact that at least 12 selective treatments were required to obtain stable mutants, indicate that: (i) such phenotypes probably can be expressed by mutations affecting one or more of the larger capsid polypeptides, and (ii) such phenotypes reflect multiple mutational steps.

  6. Antiviral Activity of Sulfated Polysaccharide of Adenanthera pavonina against Poliovirus in HEp-2 Cells

    PubMed Central

    de Godoi, Ananda Marques; Faccin-Galhardi, Lígia Carla; Lopes, Nayara; de Almeida, Raimundo Rafael; Ricardo, Nágila Maria Pontes Silva; Nozawa, Carlos; Linhares, Rosa Elisa Carvalho

    2014-01-01

    Adenanthera pavonina, popularly known as red-bead tree, carolina, pigeon's eye, and dragon's eye, is a plant traditionally used in Brazil for the treatment of several diseases. The present study aimed at evaluating the activity of sulfated polysaccharide from the Adenanthera pavonina (SPLSAp) seeds against poliovirus type 1 (PV-1) in HEp-2 cell cultures. The SPLSAp presented a cytotoxic concentration (CC50) of 500 μg/mL in HEp-2 cell cultures, evaluated by the dimethylthiazolyl-diphenyltetrazolium bromide method (MTT). The SPLSAp exhibited a significant antiviral activity, with a 50% inhibitory concentration (IC50) of 1.18 µg/mL, determined by plaque reduction assay and a high selectivity index (SI) of 423. The maximum inhibition (100%) of PV replication was found when the SPLSAp treatment was concomitant with viral infection (time 0 h), at all tested concentrations. The maximal inhibition was also found when the SPLSAp was used 1 h and 2 h postinfection, albeit at 50 μg/mL and 100 μg/mL. Therefore, we demonstrated that the SPLSAp inhibited PV growth. We also suggested that SPLSAp inhibited PV in more than one step of the replication, as the mechanism of antiviral action. We, therefore, selected the compound as a potential candidate for further development towards the control of the infection. PMID:25221609

  7. Requirements for Assembly of Poliovirus Replication Complexes and Negative-Strand RNA Synthesis

    PubMed Central

    Teterina, Natalya L.; Egger, Denise; Bienz, Kurt; Brown, David M.; Semler, Bert L.; Ehrenfeld, Ellie

    2001-01-01

    HeLa cells were transfected with several plasmids that encoded all poliovirus (PV) nonstructural proteins. Viral RNAs were transcribed by T7 RNA polymerase expressed from recombinant vaccinia virus. All plasmids produced similar amounts of viral proteins that were processed identically; however, RNAs were designed either to serve as templates for replication or to contain mutations predicted to prevent RNA replication. The mutations included substitution of the entire PV 5′ noncoding region (NCR) with the encephalomyocarditis virus (EMCV) internal ribosomal entry site, thereby deleting the 5′-terminal cloverleaf-like structure, or insertion of three nucleotides in the 3Dpol coding sequence. Production of viral proteins was sufficient to induce the characteristic reorganization of intracellular membranes into heterogeneous-sized vesicles, independent of RNA replication. The vesicles were stably associated with viral RNA only when RNA replication could occur. Nonreplicating RNAs localized to distinct, nonoverlapping regions in the cell, excluded from the viral protein-membrane complexes. The absence of accumulation of positive-strand RNA from both mutated RNAs in transfected cells was documented. In addition, no minus-strand RNA was produced from the EMCV chimeric template RNA in vitro. These data show that the 5′-terminal sequences of PV RNA are essential for initiation of minus-strand RNA synthesis at its 3′ end. PMID:11264373

  8. Glycyl-tRNA synthetase specifically binds to the poliovirus IRES to activate translation initiation

    PubMed Central

    Andreev, Dmitri E.; Hirnet, Juliane; Terenin, Ilya M.; Dmitriev, Sergey E.; Niepmann, Michael; Shatsky, Ivan N.

    2012-01-01

    Adaptation to the host cell environment to efficiently take-over the host cell's machinery is crucial in particular for small RNA viruses like picornaviruses that come with only small RNA genomes and replicate exclusively in the cytosol. Their Internal Ribosome Entry Site (IRES) elements are specific RNA structures that facilitate the 5′ end-independent internal initiation of translation both under normal conditions and when the cap-dependent host protein synthesis is shut-down in infected cells. A longstanding issue is which host factors play a major role in this internal initiation. Here, we show that the functionally most important domain V of the poliovirus IRES uses tRNAGly anticodon stem–loop mimicry to recruit glycyl-tRNA synthetase (GARS) to the apical part of domain V, adjacent to the binding site of the key initiation factor eIF4G. The binding of GARS promotes the accommodation of the initiation region of the IRES in the mRNA binding site of the ribosome, thereby greatly enhancing the activity of the IRES at the step of the 48S initiation complex formation. Moonlighting functions of GARS that may be additionally needed for other events of the virus–host cell interaction are discussed. PMID:22373920

  9. Immunogenicity and safety of combined adsorbed low-dose diphtheria, tetanus and inactivated poliovirus vaccine (REVAXIS®) versus combined diphtheria, tetanus and inactivated poliovirus vaccine (DT Polio®) given as a booster dose at 6 years of age

    PubMed Central

    Gajdos, Vincent; Soubeyrand, Benoit; Vidor, Emmanuel; Richard, Patrick; Boyer, Julie; Sadorge, Christine

    2011-01-01

    This randomized, comparative, phase-IIIb study conducted in France aimed to demonstrate whether seroprotection against diphtheria, tetanus and poliomyelitis 1 month after a single dose of REVAXIS (low-dose diphtheria) is non-inferior to seroprotection 1 month after a single dose of DT Polio (standard-dose diphtheria), both vaccines being given as a second booster to healthy children at 6 years of age. Children were randomly assigned to receive a single intramuscular dose of REVAXIS or DT Polio. Primary endpoints were the 1-month post-booster seroprotection rates for diphtheria, tetanus and poliovirus type-1, -2 and -3 antigens. Secondary endpoints were immunogenicity and safety observations. Of 788 children screened, 760 were randomized: REVAXIS group, 384 children; DT Polio group, 376 children. No relevant difference in demographic characteristics at baseline was observed between REVAXIS and DT Polio groups. Noninferiority of REVAXIS compared with DT Polio for seroprotection was demonstrated against diphtheria (respectively 98.6% and 99.3%), tetanus (respectively 99.6% and 100%) and poliovirus antigens (100% for each types in both groups). No allergic reactions to REVAXIS were reported. A benefit/risk ratio in favor of REVAXIS was suggested by the trend towards a better tolerability of REVAXIS compared with DT Polio regarding the rate of severe solicited injection-site reactions. The results support the use of REVAXIS as a booster at 6 years of age in infants who previously received a three-dose primary series within the first 6 months of life and a first booster including diphtheria, tetanus and poliovirus vaccine(s) given before 2 years of age. PMID:21441781

  10. Immunogenicity and safety of combined adsorbed low-dose diphtheria, tetanus and inactivated poliovirus vaccine (REVAXIS (®)) versus combined diphtheria, tetanus and inactivated poliovirus vaccine (DT Polio (®)) given as a booster dose at 6 years of age.

    PubMed

    Gajdos, Vincent; Soubeyrand, Benoit; Vidor, Emmanuel; Richard, Patrick; Boyer, Julie; Sadorge, Christine; Fiquet, Anne

    2011-05-01

    This randomized, comparative, phase-IIIb study conducted in France aimed to demonstrate whether seroprotection against diphtheria, tetanus and poliomyelitis 1 month after a single dose of REVAXIS (low-dose diphtheria) is non-inferior to seroprotection 1 month after a single dose of DT Polio (standard-dose diphtheria), both vaccines being given as a second booster to healthy children at 6 years of age. Children were randomly assigned to receive a single intramuscular dose of REVAXIS or DT Polio. Primary endpoints were the 1-month post-booster seroprotection rates for diphtheria, tetanus and poliovirus type-1, -2 and -3 antigens. Secondary endpoints were immunogenicity and safety observations. Of 788 children screened, 760 were randomized: REVAXIS group, 384 children; DT Polio group, 376 children. No relevant difference in demographic characteristics at baseline was observed between REVAXIS and DT Polio groups. Non-inferiority of REVAXIS compared with DT Polio for seroprotection was demonstrated against diphtheria (respectively 98.6% and 99.3%), tetanus (respectively 99.6% and 100%), and poliovirus antigens (100% for each types in both groups). No allergic reactions to REVAXIS were reported. A benefit/risk ratio in favor of REVAXIS was suggested by the trend towards a better tolerability of REVAXIS compared with DT Polio regarding the rate of severe solicited injection-site reactions. The results support the use of REVAXIS as a booster at 6 years of age in infants who previously received a three-dose primary series within the first 6 months of life and a first booster including diphtheria, tetanus and poliovirus vaccine(s) given before 2 years of age.

  11. The role of supplementary environmental surveillance to complement acute flaccid paralysis surveillance for wild poliovirus in Pakistan – 2011–2013

    PubMed Central

    Burns, Cara C.; Sharif, Salmaan; Gary, Howard E.; Iber, Jane; Henderson, Elizabeth; Malik, Farzana; Zahoor Zaidi, Syed Sohail; Shaukat, Shahzad; Rehman, Lubna; Pallansch, Mark A.; Orenstein, Walter A.

    2017-01-01

    Background More than 99% of poliovirus infections are non-paralytic and therefore, not detected by acute flaccid paralysis (AFP) surveillance. Environmental surveillance (ES) can detect circulating polioviruses from sewage without relying on clinical presentation. With extensive ES and continued circulation of polioviruses, Pakistan presents a unique opportunity to quantify the impact of ES as a supplement to AFP surveillance on overall completeness and timeliness of poliovirus detection. Methods Genetic, geographic and temporal data were obtained for all wild poliovirus (WPV) isolates detected in Pakistan from January 2011 through December 2013. We used viral genetics to assess gaps in AFP surveillance and ES as measured by detection of ‘orphan viruses’ (≥1.5% different in VP1 capsid nucleotide sequence). We compared preceding detection of closely related circulating isolates (≥99% identity) detected by AFP surveillance or ES to determine which surveillance system first detected circulation before the presentation of each polio case. Findings A total of 1,127 WPV isolates were detected by AFP surveillance and ES in Pakistan from 2011–2013. AFP surveillance and ES combined exhibited fewer gaps (i.e., % orphan viruses) in detection than AFP surveillance alone (3.3% vs. 7.7%, respectively). ES detected circulation before AFP surveillance in nearly 60% of polio cases (200 of 346). For polio cases reported from provinces conducting ES, ES detected circulation nearly four months sooner on average (117.6 days) than did AFP surveillance. Interpretation Our findings suggest ES in Pakistan is providing earlier, more sensitive detection of wild polioviruses than AFP surveillance alone. Overall, targeted ES through strategic selection of sites has important implications in the eradication endgame strategy. PMID:28742803

  12. A New Internal Ribosomal Entry Site 5′ Boundary Is Required for Poliovirus Translation Initiation in a Mouse System

    PubMed Central

    Ishii, Toshihiko; Shiroki, Kazuko; Hong, Duck-Hee; Aoki, Takahiro; Ohta, Yoshihiro; Abe, Shinobu; Hashizume, So; Nomoto, Akio

    1998-01-01

    Four mutants of the virulent Mahoney strain of poliovirus were generated by introducing mutations in nucleotides (nt) 128 to 134 of the genome, a region that contains a part of the stem-loop II (SLII) structure located within the internal ribosomal entry site (IRES; nt 120 to 590) (K. Shiroki, T. Ishii, T. Aoki, Y. Ota, W.-X. Yang, T. Komatsu, Y. Ami, M. Arita, S. Abe, S. Hashizume, and A. Nomoto, J. Virol. 71:1–8, 1997). These mutants (SLII mutants) replicated well in human HeLa cells but not in mouse TgSVA cells that had been established from the kidney of a poliovirus-sensitive transgenic mouse. Their neurovirulence in mice was also greatly attenuated compared to that of the parental virus. The poor replication activity of the SLII mutants in TgSVA cells appeared to be attributable to reduced activity of the IRES. Two and three naturally occurring revertants that replicated well in TgSVA cells were isolated from mutants SLII-1 and SLII-5, respectively. The revertants recovered IRES activity in a cell-free translation system from TgSVA cells and returned to a neurovirulent phenotype like that of the Mahoney strain in mice. Two of the revertant sites that affected the phenotype were identified as being at nt 107 and within a region from nt 120 to 161. A mutation at nt 107, specifically a change from uridine to adenine, was observed in all the revertant genomes and exerted a significant effect on the revertant phenotype. Exhibition of the full revertant phenotype required mutations in both regions. These results suggested that nt 107 of